Airway medicaments

ABSTRACT

Described herein are compositions, methods, kits and devices for the treatment and/or prevention of a wide spectrum of disease conditions. In particular, bacterial populations described herein are live, purified bacteria for the modulation, restoration and/or promotion of the microbiome in the upper respiratory tract of a subject, including the nasal cavity, to promote health. Such bacterial populations may include single or multiple strains for bacteria. The multiple strains of bacteria may be strains from the same or different species, including species of Corynebacterium and/or Dolosigranulum pigrum.

CROSS REFERENCE

This application is a Continuation of International Application No.PCT/US2021/034464 filed on May 27, 2021, which claims the benefit ofU.S. Provisional Application No. 62/704,770, filed May 28, 2020, thedisclosures of which are incorporated herein by reference in theirentirety.

BACKGROUND

Host and environmental factors influence the integrity of the microbiomein subjects. Microbial imbalance can lead to inflammation (or viceversa), resulting in opportunistic pathogenic microorganism colonizationand subsequent disease conditions. Probiotic bacteria provide atherapeutic opportunity for addressing microbiome imbalance and diseaserelated conditions. Typically, probiotic bacteria in clinicaldevelopment to date have focused on gut colonizing bacteria. In someinstances, there may be a need for forms of intervention which promotean improved microbiome environment in the upper respiratory tract, inparticular the nasal cavity, for the treatment and prevention ofconditions in the nasal cavity as well as in systems linked to the upperrespiratory tract by a shared mucosal network, such as the lowerrespiratory tract and central nervous system. In addition, side effectsof many current therapies (e.g., chemotherapy and radiation therapy) canincrease inflammation and harm the microbiome of the airway system.

BRIEF SUMMARY

Provided herein are compositions, including pharmaceutical compositions,methods, kits and devices for modification of microbiome in a subject.As described in more detail herein, such compositions provide for, amongother things, defending the integrity of the nasal cavity microbiome,and beneficially imparting downstream effects on the upper respiratorytract (including the nasal cavity), lower respiratory tract (includingthe lung), and central nervous system (including the olfactory system)for the prevention and/or treatment of disease conditions. Furtherprovided herein are mixtures of live, purified bacterial strainsaffording various bactericidal mechanisms to pathogenic bacteria, and insome instances the live, purified bacteria are mutualistic in theirrelationship to each other. In some embodiments, the live, purifiedbacteria are selected from Corynebacterium species and, optionally,Dolosigranulum species. In some embodiments, the live, purified bacteriaare species of Corynebacterium and/or Dolosigranulum. In someembodiments, the live, purified bacteria comprise a strain listed inTable 1 and/or Table 2. In some embodiments, the Corynebacterium speciesis C. pseudodiphtheriticum, C. accolens, C. amycolatum, C. propinquum,C. glutamicum, or C. striatum. In some embodiments, the Corynebacteriumspecies is a combination of at least two species selected from C.pseudodiphtheriticum, C. accolens, C. amycolatum, C. propinquum, C.glutamicum, and C. striatum. In some embodiments, the Corynebacteriumspecies is C. pseudodiphtheriticum. In some embodiments, the compositioncomprises at least two strains of C. pseudodiphtheriticum. In someembodiments, the Corynebacterium species is C. pseudodiphtheriticum andthe Dolosigranulum species is D. pigrum. Further provided herein arecompositions wherein the live, purified bacteria comprise bacteriahaving a high percent identity, e.g., at least 97% identity, based oncomparison to whole genome, the entire 16S rRNA region, or ahypervariable region of the 16S rRNA (e.g., V4 region), to a bacterialstrain listed in Table 1 or Table 2.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 : Illustrates, in some embodiments, various dosage formsdescribed herein for oral 101 and/or intranasal 102 administration.Dosage forms illustrated include an inhaler 103 for aerosoladministration, liquid 104 and capsule 105 for oral administration, anda spray bottle 106 for intranasal administration.

FIG. 2A, in some embodiments, illustrates a plot of OD600 measurementsfrom growth of ATCC 10700, with OD600 for the Y axis and time in hourson the X axis.

FIG. 2B, in some embodiments, illustrates a plot of OD600 measurementsfrom growth of ATCC 10700, with Log(OD600) for the Y axis and time inhours on the X axis.

FIG. 3A, in some embodiments, illustrates a plot of OD600 measurementsfrom growth of JCM 1320, with OD600 for the Y axis and time in hours onthe X axis.

FIG. 3B, in some embodiments, illustrates a plot of OD600 measurementsfrom growth of JCM 1320, with Log(OD600) for the Y axis and time inhours on the X axis.

FIG. 4A, in some embodiments, illustrates a plot of OD600 measurementsfrom growth of cultures having varying amounts of ATCC 10700 and JCM1320, with OD600 for the Y axis and time in hours on the X axis.

FIG. 4B, in some embodiments, illustrates a plot of OD600 measurementsfrom growth of cultures having varying amounts of ATCC 10700 and JCM1320, with Log(OD600) for the Y axis and time in hours on the X axis.

FIG. 5 , in some embodiments, is an image capture of an agar plate,showing four spottings of ATCC 10700 on the left, and four spottings ofJCM 1320 on the right. The image capture was taken after 24 hours ofgrowth.

FIG. 6 , in some embodiments, is an image capture of an agar plate,showing columns of left to right with two spottings of ATCC 10700, twospottings of D. pigrum, two spottings of D. pigrum, and two spottings ofJCM 1320. The image capture was taken after 24 hours of growth.

DETAILED DESCRIPTION

Provided herein are composition, methods, kits and devices relating toupper respiratory tract colonizing bacteria for prevention and/ortreatment of respiratory tract conditions and/or neurologicalconditions. Furthermore, provided herein are (1) probiotic bacterialmixtures (2) excipients, dosage forms and routes of administration forsuch mixtures, (3) and conditions for treatment with such probioticbacterial mixtures.

Throughout this disclosure, various embodiments are presented in a rangeformat. It should be understood that the description in range format ismerely for convenience and brevity and should not be construed as aninflexible limitation on the scope of any embodiments. Accordingly, thedescription of a range should be considered to have specificallydisclosed all the possible subranges as well as individual numericalvalues within that range to the tenth of the unit of the lower limitunless the context clearly dictates otherwise. For example, descriptionof a range such as from 1 to 6 should be considered to have specificallydisclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual valueswithin that range, for example, 1.1, 2, 2.3, 5, and 5.9. The upper andlower limits of these intervening ranges may independently be includedin the smaller ranges, and are also encompassed within the invention,subject to any specifically excluded limit in the stated range. Wherethe stated range includes one or both of the limits, ranges excludingeither or both of those included limits are also included, unless thecontext clearly dictates otherwise.

The terminology used herein is for the purpose of describing particularinstances only and is not intended to be limiting of any embodiment. Asused herein, the singular forms “a,” “an” and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. As used herein, the term “and/or” includes any and allcombinations of one or more of the associated listed items.

Unless specifically stated or obvious from context, as used herein, theterm “about” in reference to a number or range of numbers is understoodto mean the stated number and numbers +/−10% thereof, or 10% below thelower listed limit and 10% above the higher listed limit for the valueslisted for a range.

The term “subject” as used herein includes human and non-human mammals,including for example: a primate, cow, horse, pig, sheep, goat, dog,cat, or rodent, capable of being colonized by other organisms.

In some embodiments, provided herein are compositions which includebacteria having a percent identity based on 16S rRNA bacterial geneticsequence, a hypervariable region of the 16S rRNA, or whole genomecomparison to a reference strain. Typically, comparison of the 16S rRNAbacterial genetic sequence allows a strain to be identified as withinthe same species as another strain by comparing sequences with knownbacterial DNA sequences using NCBI BLAST search. The level of identityin relation to a nucleotide sequence may be determined for at least 20contiguous nucleotides, for at least 30 contiguous nucleotides, for atleast at least 40 contiguous nucleotides, for at least 50 contiguousnucleotides, for at least 60 contiguous nucleotides, or for at least 100contiguous nucleotides. In some embodiments, the level of identity inrelation to a nucleotide sequence is determined for the entire sequencesearched. Percent identity may be at least 70%, 80%, 85%, 90%, 91%, 92%,93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% to a reference bacterial 16SrRNA sequence, 16S rRNA V4 region sequence, or whole genome sequence.Percent identity may be at least 70%, 80%, 85%, 90%, 91%, 92%, 93%, 94%,95%, 96%, 97%, 98%, 99%, or 100% to a reference bacteria 16S rRNA: V1region, V2 region, V3 region, V5 region, V6 region, V7 region, V8 regionor V9 region sequence.

In some embodiments, a live bacterium can comprise a bacterium thatretains membrane stability. In some embodiments, a live bacterium cancomprise a bacterium that is capable of transcription and translation.In some embodiments, a live bacterium can comprise a bacterium that iscapable of cell division. In some embodiments, live bacteria can bedetermined by a culture dependent or a culture independent technique. Insome cases, live bacteria can comprise an individual or a group ofbacteria that can produce a colony-forming unit (cfu) when plated onstable growth media. In some embodiments, live and/or dead bacteria canbe determined by imaging, for example with a live/dead stain. In someembodiments, a viability PCR based method can be used to determine livebacteria. In some cases, a metabolomic assay can be used to determinelive bacteria.

In some embodiments, reference to a population of bacteria or a purifiedpopulation refers to a plurality of bacteria.

1) Probiotic Bacterial Mixtures

The nasal cavity of the upper respiratory tract is a nutrient-poor,high-salinity niche where bacteria compete for limited resources. Ahealthy nasal microbiome prevents pathogenic microorganisms fromcolonization, harmful products from such colonization, inflammation, andgeneration of “leaky” cell-cell junctions, all of which can result insubsequent disease conditions in other organs along a shared mucosalnetwork, including the lungs and central nervous system (CNS). Withregard to CNS, many neurological disorders are associated with olfactorysystem functional impairment, such as loss of smell. The olfactory nerve(cranial nerve I) is the shortest cranial nerve, where cell bodies ofprimary olfactory neurons are found in the neuroepithelium and theirdendrites extend into the nasal cavity. Injury to the olfactoryepithelium, such as through pathogen- or chemical-induced damage, canlead to removal of the protective mucosal barrier and death of olfactoryneurons, resulting in open channels from the olfactory epithelium to thebulb, creating an avenue for pathogens or their produces materials tosidestep the blood brain barrier. Thus, the nasal cavity provides anopportunity for imparting beneficial microbiome change to prevent and/ortreat many disease conditions. For example, in a small human trial, abeneficial strain of Corynebacterium pseudodiphtheriticum (C.pseudodiphtheriticum strain “090104”) has been reported to show efficacyin elimination of Staphylococcus aureus from the nasal cavity involunteers exposed to abnormal microclimate and altered gaseousenvironment, Kiryukhina et al. Probiotics and Antimicrobial Proteins(2013). Nasal spray application of the strain eradicated S. aureus inthree subjects and reduced its presence in a methicillin-resistant S.aureus (MRSA) carrier.

Bacteria described herein are to be used to control, treat, reduce,eliminate, and/or prevent pathogenic colonization by an organism on asubject and/or reduce inflammation. Compositions described herein may beadministered or designed for delivery to particular locations of thesubject, in particular, the upper respiratory tract, including theanterior nares, nasal cavity, and/or nasopharynx. Bacterial strainsdescribed herein may be isolated from the upper respiratory tractregions including, without limitation, anterior nares, nasal cavity,and/or nasopharynx.

In some embodiments, provided herein are compositions having bacterialpopulations having one or more species, and one or more strains for eachof the one or more species. In some instances, a composition describedherein includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more species ofbacteria. In some instances, a composition described herein includes 1,2, 3, 4, 5, 6, 7, 8, 9, 10 or more strains of bacteria. Further providedherein are bacterial populations comprising at least one species ofCorynebacterium. Further provided herein are bacterial populationscomprising a plurality of species of Corynebacterium. Corynebacteriumare gram-stain-positive bacteria, non-spore forming and nonmotile.Exemplary Corynebacterium species for inclusion in compositionsdescribed herein include: C. accolens, C. afermentans, C. ammoniagenes,C. amycolatum, C. argentoratense, C. aquaticum, C. auris, C. bovis, C.diphtheria, C. equi (now Rhodococcus equi), C. efficiens, C. flavescens,C. glucuronolyticum, C. glutamicum, C. granulosum, C. haemolyticum, C.halofytica, C. kroppenstedtii, C. jeikeium, C. macginleyi, C.matruchotii, C. minutissimum, C. parvum (Propionibacterium acnes), C.paurometabolum, C. propinquum, C. pseudodiphtheriticum (C. hofmannii),C. pseudotuberculosis, C. ovis, C. pyogenes—Trueperella pyogenes, C.urealyticum, C. renale, C. spec, C. striatum, C. tenuis, C. ulcerans, C.urealyticum, and C. xerosis. In some instances, a composition describedherein comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 of the Corynebacteriumstrains listed in Table 1. In some embodiments, a population of bacteriadescribed herein comprises a Corynebacterium strain having a 16S rRNAsequence of at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100%identity to that of a strain listed in Table 1. In some embodiments, apopulation of bacteria described herein comprises a Corynebacteriumstrain having a 16S rRNA sequence of at least 97% sequence identity withthat of a strain listed in Table 1. The sequence identity may be basedon a 16s rRNA sequence, 16s rRNA hypervariable region sequence, such asV4, or whole genome comparison. The population of bacteria may be partof a pharmaceutical composition. The bacteria may be live and purified.

TABLE 1 Corynebacterium strains Species Strain name Reference or DepositC. pseudodiphtheriticum KPL1989 GenBank: AXLR01000000 C.pseudodiphtheriticum DSM44287 GenBank: GCA_000688415.1 ATCC 10700 C.pseudodiphtheriticum 090104 GenBank: AVFF01000000 JCM 1320 C. accolensKPL1818 GenBank: AXMA01000001.1 C. accolens DSM 44278 ATCC 49725 C.amycolatum DSM6922 ATCC 49368 C. amycolatum DSM1567 MN175937 C.propinquum DSM44285 GCA_000375525.1 C. glutamicum DSM20300 ATCC 13032 C.striatum DSM20668 ATCC 6940

In some embodiments, provided herein are bacterial populationscomprising at least one species of Dolosigranulum. Further providedherein are bacterial populations comprising a plurality of species ofDolosigranulum. In some embodiments, provided herein are populations ofbacteria comprising at least one strain of Dolosigranulum pigrum. Insome instances, a composition described herein comprises 1, 2, 3, 4, 5,6, 7, 8, 9, 10 of the D. pigrum strains listed in Table 2. In someembodiments, a population of bacteria described herein comprises a D.pigrum strain having a 16S rRNA sequence of at least 90, 91, 92, 93, 94,95, 96, 97, 98, 99, or 100% sequence identity to that of a strain listedin Table 2. In some embodiments, a population of bacteria describedherein comprises a D. pigrum strain having a 16S rRNA sequence of atleast 9700 sequence identity with that of a strain listed in Table 2.The sequence identity may be based on a 16s rRNA sequence, 16s rRNAhypervariable region sequence, such as V4, or whole genome comparison.The population of bacteria may be part of a pharmaceutical composition.The bacteria may be live and purified.

TABLE 2 Dolosigranulum strains Species Strain name Reference or DepositD. pigrum KLP1914 Brugger et al., BioRxiv (2019). D. pigrum CDC 39-95LaClaire and Facklam, 2000 D. pigrum CDC 2949-98 LaClaire and Facklam,2000 D. pigrum CDC 4294-98 LaClaire and Facklam, 2000 D. pigrum CDC4420-98 LaClaire and Facklam, 2000 D. pigrum CDC 4545-98 LaClaire andFacklam, 2000 D. pigrum CDC 4709-98 LaClaire and Facklam, 2000 D. pigrumCDC 4199-99 LaClaire and Facklam, 2000 D. pigrum CDC 4791-99 LaClaireand Facklam, 2000 D. pigrum CDC 4792-99 LaClaire and Facklam, 2000 D.pigrum AMBR11 LMG P-31 124 D. pigrum AMBR12 LMG P-31 154

Further provided herein are populations of bacteria for colonization tothe upper respiratory tract having a combination of strains includingstrains, from different species. In some embodiments, the populations ofbacteria comprise at least one strain of Corynebacterium, and at leastone strain of Dolosigranulum. In some embodiments, the populations ofbacteria comprise at least one strain of C. pseudodiphtheriticum and atleast one strain of D. pigrum. In some embodiments, the populations ofbacteria comprise at least one strain listed in Table 1, and at leastone strain listed in Table 2. In some embodiments, the populations ofbacteria comprise at least one strain having a 16S rRNA sequence of atleast 9700 sequence identity with that of a strain listed in Table 1,and at least one strain having a 16S rRNA sequence of at least 97%sequence identity with that of a strain listed in Table 2. In furtherembodiments, 1, 2, 3 or more of the Corynebacterium strains are C.pseudodiphtheriticum strains. The population of bacteria may be part ofa pharmaceutical composition. The bacteria may be live and purified.Compositions described herein may have mixtures of species. The mixturesmay be up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more species and mayinclude species listed in Table 1 and/or Table 2. Such species may bepresent in equal amounts or varied amounts. In some embodiments, eachdifferent species is present in at least 1%, 10%, 15%, 20%, 25%, 30%,35%, 40%, 45%, 50%, or 100% of the total colony forming units (CFUs) forthe total CFUs for the population of bacteria. Compositions describedherein may have mixtures of strains within a species. The mixtures maybe up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more strains and may be from aspecies listed in Table 1 and/or Table 2. Such strains may be present inequal amounts or varied amounts. In some embodiments, different strainsare present in at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, or100% of the total colony forming units (CFUs) for the total CFUs for thepopulation of bacteria.

In some embodiments, when administered to a subject, bacterialpopulations described herein reduce or eliminate colonization in therespiratory tract of pathogenic bacteria. Exemplary respiratory tractpathogenic bacteria include, without limitation, Staphylococcus aureus,Streptococcus pneumoniae, Pseudomonas aeruginosa, and Burkholderiapseudomallei. Exemplary strains of such pathogenic bacteria are listedin Table 3. Such reduction of pathogenic bacteria may be in the upperrespiratory tract or the lower respiratory tract.

TABLE 3 Pathogenic bacteria Species Strain name Reference S. aureus(MRSA) JE2 BEI Resources NR-46543 S. aureus (MRSA) LAC ATCC BAA-1556 S.aureus (MRSA) Mu50 ATCC 700699 S. aureus (MSSA) 96:308/ ATCC BAA-1749USA900 S. pneumoniae TIGR4 ATCC BAA-33 S. pneumoniae M270-8 ATCCBAA-1659 S. pneumoniae DBL5 AF071810 Pseudomonas ATCC 27853 aeruginosaBurkholderia MSHR520 GenBank: pseudomallei GCA_000583835.12) Excipients, Dosage Forms and Routes of Administrations

To facilitate administration, pharmaceutical compositions describedherein may include one or more pharmaceutically acceptable excipients.Example pharmaceutically acceptable excipients include, withoutlimitation, diluents, adjuvants, excipients, water, oils (includingpetroleum, animal, vegetable or synthetic oils). Further examplesinclude saline, gum acacia, gelatin, starch paste, talc, keratin,colloidal silica, and urea. Such excipients may include binders such asethyl cellulose, carboxymethylcellulose, microcrystalline cellulose, orgelatin; excipients such as starch, lactose or dextrins; disintegratingagents such as alginic acid, sodium alginate, Primogel, and cornstarch;lubricants such as magnesium stearate or Sterotex; glidants such ascolloidal silicon dioxide; sweetening agents such as sucrose orsaccharin, a flavoring agent such as peppermint, methyl salicylate ororange flavoring, or coloring agents. Further examples of excipientsinclude polyethylene glycol, cyclodextrin, oils, or any other similarliquid carrier that may be formulated into a capsule. Still furtherexamples of excipients include sterile diluents such as water, salinesolution, physiological saline, Ringer's solution, isotonic sodiumchloride, fixed oils such as synthetic mono or diglycerides,polyethylene glycols, glycerin, cyclodextrin, propylene glycol or othersolvents; antibacterial agents such as benzyl alcohol or methyl paraben;antioxidants such as ascorbic acid or sodium bisulfite; chelating agentssuch as ethylenediaminetetraacetic acid; buffers such as acetates,citrates or phosphates and agents for the adjustment of tonicity such assodium chloride or dextrose, thickening agents, lubricating agents, andcoloring agents. In some embodiments of the invention, thepharmaceutically acceptable carrier can comprise a growth medium thatcan support the growth and/or static existence of beneficial bacteriadescribed herein in the context of the pharmaceutical composition priorto administration of the pharmaceutical composition to the subject.

In some instances, a pharmaceutical composition described hereinincludes materials capable of modifying the physical form of a dosageunit. For example, various dosage forms described herein are illustratedin FIG. 1 for oral 101 and/or intranasal 102 administration. Dosageforms for compositions described herein include a nebulizer or inhaler103 for aerosol administration, liquid 104 and capsule 105 for oraladministration, and a spray bottle 106 for intranasal administration. Insome instances, a pharmaceutical composition described herein is locatedwithin a nasal spray bottle. In some instances, a pharmaceuticalcomposition described herein is prepared as an aerosol. Aerosolsencompass a variety of systems including colloids and pressurizedpackages. Delivery of a composition in this form may include propulsionof a pharmaceutical composition including the beneficial bacteriadescribed herein through use of liquefied gas or other compressed gas orby a suitable pump system. Aerosols may be delivered in single phase,bi-phasic, or triphasic systems. Compositions, including pharmaceuticalcompositions, described herein may be formulated depending on the routeof administration. Such forms include, without limitation, solutions,suspensions, emulsions, cream, gel, lotion, ointment, tablets, tabs,films, pills, pellets, capsules, capsules including liquids, powders,sustained-release formulations, directed release formulations,lyophylates (freeze dried/lyophilized), emulsions, aerosols, sprays,granules, powders, or syrups. Dosage forms may be, without limitation,liquid, a solid, semisolid, gel, or aerosol. Methods of administrationinclude, but are not limited to, oral, intranasal, or by inhalation.Pharmaceutical compositions described herein may include kits wherebacteria described herein are included in a first container (e.g.,lyophilized cells), and one or more pharmaceutical acceptable excipientsare included in a second container (e.g., water). In some embodiments,provided herein are kits, wherein the kit comprises: a first container,wherein the first container comprises live, purified, and lyophilizedpopulation of bacteria that comprises: a plurality of strains ofCorynebacterium pseudodiphtheriticum; and a second container, whereinthe second container comprises a pharmaceutically acceptable excipient.In some embodiments, provided herein are kits, wherein the kitcomprises: a first container, wherein the first container compriseslive, purified, and lyophilized population of bacteria that comprises: aplurality of species of Corynebacterium; and a second container, whereinthe second container comprises a pharmaceutically acceptable excipient.In some embodiments, provided herein are kits, wherein the kitcomprises: a first container, wherein the first container compriseslive, purified, and lyophilized population of bacteria that comprises: aplurality of strains of Dolosigranulum pigrum; and a second container,wherein the second container comprises a pharmaceutically acceptableexcipient. In some embodiments, provided herein are kits, wherein thekit comprises: a first container, wherein the first container compriseslive, purified, and lyophilized population of bacteria that comprises: aplurality of strains of Corynebacterium pseudodiphtheriticum; and aplurality of strains of Dolosigranulum pigrum and; and a secondcontainer, wherein the second container comprises a pharmaceuticallyacceptable excipient. In some embodiments, provided herein are kits,wherein the kit comprises: a first container, wherein the firstcontainer comprises live, purified, and lyophilized population ofbacteria present in a total amount of at least 10{circumflex over ( )}3cfu that comprises: a strain of Corynebacterium pseudodiphtheriticum;and a strain of Dolosigranulum pigrum; and a second container, whereinthe second container comprises a pharmaceutically acceptable excipient.Further provided herein are kits, wherein the live, purified, andlyophilized population of bacteria is present in a total amount of up to10{circumflex over ( )}15 cfu. Further provided herein are kits, whereinthe live, purified, and lyophilized population of bacteria is present ina total amount of 10{circumflex over ( )}3 to 10{circumflex over ( )}12cfu.

Dosing may include single or multiple administrations of pharmaceuticalcompositions described herein. Examples include: multiple times a day,daily, every other day, 1, 2, 3, 5, 6, or 7 times a week, weekly, orless often, a single administration, a course of treatment involvingseveral treatments on a regular or irregular basis, or multipleadministrations for a period of time until a diminution of colonizationis achieved. In some cases, dosing can occur every day, 2 days, 3 days,4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 1month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8months, 9 months, 10 months, 11 months, 1 year, 2 years, or as needed.The dosing regimen, including the regularity of and mode ofadministration, may be dependent on factors including but not limited tothe subject being treated; the severity of the condition; the manner ofadministration, the stage of colonization, the presence of one or moreother conditions such as pregnancy, infancy, or the presence of one ormore additional diseases. In some embodiments, the subject is an infant.The infant can be up to 24 months old. In some embodiments, the subjectis a child. The child may be 2 years to 21 years old. In someembodiments, the subject is an adult. Adults may be 21 years old ormore. In some embodiments, the adult is of advanced age, such as 65years or older.

Compositions, including pharmaceutical compositions, described hereinmay comprise a single (unit) dose of bacteria. Compositions describedherein may comprise about 10² to about 10¹⁵ colony forming units (cfu)of bacteria or a bacterial strain described herein. Compositionsdescribed herein may comprise about: 10² to 10¹² cfu, 10³ to 10¹² cfu,10³ to 10¹¹ cfu, 10³ to 10¹⁰ cfu, 10³ to 10⁹ cfu, 10³ to 10 cfu, 10³ to10⁷ cfu, 10³ to 10⁶ cfu, 10³ to about 10⁵ cfu, 10³ to 10⁴ cfu, 10⁴ to10¹² cfu, 10⁴ to 10¹¹ cfu, 10⁴ to 10¹⁰ cfu, 10⁴ to 10⁹ cfu, 10⁴ to 10⁸cfu, 10⁴ to 10⁷ cfu, 10⁴ to 10⁶ cfu, 10⁵ to 10¹² cfu, 10⁵ to 10¹¹ cfu,about 10⁵ to about 10¹⁰ cfu, 10⁶ to 10¹² cfu, 10⁷ to 10¹² cfu, 10⁸ to10¹² cfu, 10⁹ to 10¹² cfu, 10¹⁰ to 10¹² cfu, 10¹¹ to 10¹² cfu, or 106 to10¹⁰ cfu of bacteria or a bacterial strain described herein. In someembodiments, compositions comprise about 10³ cfu, about 10⁴ cfu, about10⁵ cfu, about 10⁶ cfu, about 10⁷ cfu, about 10⁸ cfu, about 10⁹ cfu,about 10¹⁰ cfu, about 10¹¹ cfu, or about 10¹² cfu of bacteria or abacterial strain described herein.

Compositions, including pharmaceutical compositions, described hereinmay comprise 10² to 10¹⁵ colony forming units (cfu) of bacteria or abacterial strain described herein per mL. Compositions described hereinmay comprise about 10² to 10¹² cfu, 10³ to 10¹² cfu, 10³ to 10¹¹ cfu,10³ to 10¹⁰ cfu, 10³ to 10⁹ cfu, 10³ to 10¹ cfu, 10³ to 10⁷ cfu, 10³ to10⁶ cfu, 10³ to about 10⁵ cfu, 10³ to 10⁴ cfu, 10⁴ to 10¹² cfu, 10⁴ to10¹¹ cfu, 10⁴ to 10¹⁰ cfu, 10⁴ to 109 cfu, 10⁴ to 101 Cfu, 10⁴ to 10⁷cfu, 10⁴ to 10⁶ cfu, 10⁵ to 10¹² cfu, 10⁵ to 10¹¹ cfu, about 10⁵ toabout 10¹⁰ cfu, 10⁶ to 10¹² cfu, 10⁷ to 10¹² cfu, 10⁸ to 10¹² cfu, 10⁹to 10¹² cfu, 10¹⁰ to 10¹² cfu, 10¹¹ to 10¹² cfu, or 106 to 10¹⁰ cfu ofbacteria or a bacterial strain described herein per mL.

Compositions described herein may comprise may at least about 0.01% byweight, at least about 0.05% by weight, at least about 0.1% by weight,at least about 0.2% by weight, at least about 0.3% by weight, at leastabout 0.4% by weight, at least about 0.5% by weight, at least about 0.6%by weight, at least about 0.7% by weight, at least about 0.8% by weight,at least about 0.9% by weight, at least about 1.0% by weight, at leastabout 1.5% by weight, at least about 2.0% by weight, at least about 3.0%by weight, at least about 4.0% by weight, at least about 5.0% by weight,at least about 6.0% by weight, at least about 7.0% by weight, at leastabout 8.0% by weight, at least about 9.0% by weight, at least about10.0% by weight, at least about 11.0% by weight, at least about 12.0% byweight, at least about 13.0% by weight, at least about 14.0% by weight,at least about 15.0% by weight, at least about 16.0% by weight, at leastabout 17.0% by weight, at least about 18.0% by weight, at least about19.0% by weight, at least about 2.0% by weight, at least about 25.0% byweight, at least about 3.0% by weight, at least about 35.0% by weight,at least about 40.0% by weight, at least about 45.0% by weight, or atleast about 50.0% by weight of bacteria or bacterial strain describedherein. In some embodiments, compositions can include from 0.01% to 30%by weight, from about 0.01% to 20% by weight, from 0.01% to 5% byweight, from 0.1% to 30% by weight, from 0.1% to 20% by weight, from0.1% to about 15% by weight, from 0.1% to 10% by weight, from 0.1% to 5%by weight, from 0.2% to 5% by weight, from 0.3% to 5% by weight, from0.4% to 5% by weight, from 0.5% to 5% by weight, or from 1% to 5% byweight of bacteria or bacterial strain described herein.

Compositions, including pharmaceutical compositions, described hereinmay comprise a ratio (cfu to cfu) of about: 1:1, 1:2, 1:3, 1:4, 1:5,1:6, 1:7, 1:8, 1:9, 1:10, 1:20, 1:30, 1:40, 1:50, 1:60, 1:70, 1:80,1:90, 1:100, 1:200, 1:300, 1:400, 1:500, 1:600, 1:700, 1:800, 1:900 orabout 1:1000 of a strain in Table 1 to another strain in Table 1 or astrain in Table 2 to another strain in Table 2. Compositions, includingpharmaceutical compositions, described herein may comprise a ratio (cfuto cfu) of about: 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10,1:20, 1:30, 1:40, 1:50, 1:60, 1:70, 1:80, 1:90, 1:100, 1:200, 1:300,1:400, 1:500, 1:600, 1:700, 1:800, 1:900 or about 1:1000 of a strain inTable 1 to a strain in Table 2. Compositions, including pharmaceuticalcompositions, described herein may comprise a ratio (cfu to cfu) ofabout: 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:20, 1:30,1:40, 1:50, 1:60, 1:70, 1:80, 1:90, 1:100, 1:200, 1:300, 1:400, 1:500,1:600, 1:700, 1:800, 1:900 or about 1:1000 of multiple strains ofCorynebacterium and/or Dolosigranulum pigrum.

3) Conditions

In some embodiments, provided herein are compositions for the preventionor treatment of a condition of the respiratory tract. As described inmore detail herein, such conditions are of the upper and/or lowerrespiratory tract. The upper airways or upper respiratory tractgenerally includes the nose and nasal passages, paranasal sinuses, thepharynx, and the portion of the larynx above the vocal folds (cords).The lower airways or lower respiratory tract generally includes theportion of the larynx below the vocal folds, trachea, and the bronchi,bronchioles, and alveoli, which make up the lungs. These structures pullin air from the upper respiratory system, absorb the oxygen, and releasecarbon dioxide in exchange. In some embodiments, compositions describedcomprise beneficial bacteria present in an amount sufficient for areduction in incidence of colonization of a pathogenic bacteria. In someembodiments, the condition relates to a bacterial infection. Sources forbacterial infections for prevention or treatment with pharmaceuticalcompositions described herein include, without limitation, S. aureus(methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S.aureus (MSSA)), S. pneumoniae, Pseudomonas aeruginosa, and Bordetellapertussis. Upper respiratory tract conditions for treatment orprevention following administration of composition described hereininclude, without limitation, allergic rhinitis or non-allergic rhinitis,including acute bacterial rhinosinusitis. Lower respiratory tractconditions for treatment or prevention following administration ofcomposition described herein include, without limitation, asthma,tuberculosis, whooping cough (pertussis), pneumonia (includinghospital-acquired pneumonia (HAP), ventilator-associated pneumonia(VAP), and community acquired pneumonia (CAP)), walking pneumonia, andbronchitis, lung cancer, cystic fibrosis, chronic obstructive pulmonarydisease (COPD) (e.g., emphysema or chronic bronchitis), idiopathicpulmonary fibrosis (IPF), and interstitial lung disease (ILD). In someembodiments, a pharmaceutical composition described herein isadministered to a S. aureus positive subject, optionally prior to,receiving a ventilator therapy. In further embodiments, the subject isdiagnosed with COVID. In some embodiments, a pharmaceutical compositiondescribed herein is administered to a coronavirus (CoV) positive subject(e.g., SARS-CoV-2, SARS-CoV Tor2, and MERS-CoV), optionally prior to,receiving a ventilator therapy. In some embodiments, the asthma ischildhood asthma, adult onset asthma, occupational asthma, severeasthma, or seasonal asthma. In some embodiments, the lung cancer issmall cell lung cancer or non-small cell lung cancer (NSCLC), includingadenocarcinoma, squamous cell carcinoma, or large cell carcinoma.Exemplary lung cancers include, without limitation, primary pulmonarylymphoma, lymphangitic carcinomatosis, epithelioid hemangioendothelioma,or multiple cystic lung disease (MCLD), sarcomatoid carcinoma,adenosquamous carcinoma, salivary gland-type lung carcinoma, large cellneuroendocrine carcinoma, granular cell lung tumour, carcinoids, oratypical carcinoids. In some embodiments, the cancer is a lip cancer,tongue cancer, mouth cancer, oral cavity cancer, oropharyngeal cancer.Example cancers in this region include, without limitation, laryngealcancer, nasopharyngeal cancer, oral squamous cell carcinoma,oropharyngeal squamous cell carcinoma, otic tumors, salivary glandtumors, and paranasal sinus cancer. In some embodiments, apharmaceutical composition provided herein is an adjuvant to a treatmentof respiratory conditions described herein. In some embodiments, canceris stage I, II, III or IV. In some embodiments, the cancer ismetastatic. In some embodiments, a pharmaceutical composition describedherein is an adjuvant to chemotherapy for treatment of cancer. In someembodiments, the cancer is a solid cancer or hematopoietic cancer.Exemplary solid cancers include, without limitation, carcinoma andsarcoma. Exemplary hematopoietic cancers include, without limitation,leukemias, myelomas and lymphomas (including Hodgkin lymphomas, ornon-Hodgkin lymphomas (NHLs)). Example chemotherapy agents include,without limitation, etoposide optionally with a platinum agent(cisplatin or carboplatin), 5-fluorouracil (5-FU), paclitaxel,docetaxel, hydroxyurea, methotrexate, bleomycin, and capecitabine. Insome embodiments, at least one chemotherapy agent is used. In someembodiments, radiation (ionizing radiation) is administered. In someembodiments, radiation (ionizing radiation) and chemotherapy areadministered. Therapies such as chemotherapy and radiation can induce aninflammatory response and compromise integrity of cell-cell junctionsresulting in additional disease conditions, such as oral mucositis. Insome embodiments, a pharmaceutical composition described herein isadministered as an adjuvant with one or more checkpoint inhibitors fortreatment of a cancer. Exemplary checkpoint inhibitors include, withoutlimitation, anti-CTLA-4 antibody (e.g., ipilimumab), anti-PD-L1 antibody(e.g., atezolizumab), and anti-PD-1 antibody (e.g., nivolumab andpembrolizumab). In some embodiments, a pharmaceutical compositiondescribed herein is administered as treatment for a viral condition, oras an adjuvant to a therapy for treatment of a viral condition. Infurther embodiments, the virus is a virus of the respiratory tract.Exemplary virus of the respiratory tract include, without limitation,influenza A (e.g., H1N1 and H1N5), influenza B, an adenovirus,respiratory syncytial virus (RSV), enterovirus (EVs), human rhinovirus(HRV), human metapneumovirus (HMPV), human bocavirus (HBoV), coronavirus(CoV) (e.g., SARS-CoV-2, SARS-CoV Tor2, and MERS-CoV), and parainfluenzavirus (PIV). Exemplary therapies for viral conditions include, withoutlimitation, oseltamivir, zanamivir, ribavirin, palivizumab, and aspirin.In some embodiments, a pharmaceutical composition described herein isadministered to a SARS-CoV-2 positive subject, optionally prior to,receiving a ventilator therapy. In some embodiments, a pharmaceuticalcomposition used to treat or prevent a respiratory condition describedherein comprises at least one species (or strain) listed in Table 1 orTable 2, or a mixture listed in Tables 4-7. In some embodiments, apharmaceutical composition described herein is administered to a subjecthaving a respiratory condition, optionally prior to, receiving aventilator therapy. In some embodiments, a pharmaceutical compositionused to treat or prevent a respiratory condition described hereincomprises a strain of C. pseudodiphtheriticum and, optionally, a strainof D. pigrum. In some embodiments, a method for treating nasalcolonization by at least one pathogenic microorganism in a subject isprovided, the method comprising the steps of: administering apharmaceutical composition to the subject, wherein the pharmaceuticalcomposition comprises a Corynebacterium strain listed in Table 1, and aDolosigranulum strain listed in Table 2. In some embodiments, a methodfor treating nasal colonization by at least one pathogenic microorganismin a subject is provided, the method comprising the steps of:administering a pharmaceutical composition to the subject, wherein thepharmaceutical composition comprises a C. pseudodiphtheriticum strainlisted in Table 1, and a Dolosigranulum strain listed in Table 2, or amixture listed in Tables 4-7. In some embodiments, provided herein aremethods for reducing colonization of a subject's anterior nares or nasalcavity by a pathogenic microorganism, the method comprising the stepsof: administering to a subject having a pathogenic microorganism in thesubject's anterior nares or nasal cavity, a live, purified population ofbacteria, wherein the live, purified population of bacteria comprises aplurality of strains of Corynebacterium pseudodiphtheriticum. Furtherprovided herein are methods wherein the pathogenic microorganismcomprises Staphylococcus aureus, Streptococcus pneumoniae, orPseudomonas aeruginosa. Further provided herein are methods wherein thelive, purified population of bacteria comprises a mixture listed inTables 4-7. Further provided herein are methods wherein the live,purified population of bacteria comprises a mixture listed in Tables4-7. Further provided herein are methods wherein the plurality ofstrains of C. pseudodiphtheriticum comprises JCM 1320 or ATCC 10700.Further provided herein are methods wherein the plurality of strains ofC. pseudodiphtheriticum comprises JCM 1320 and ATCC 10700. Furtherprovided herein are methods wherein the plurality of strains of C.pseudodiphtheriticum comprises strains selected from a strain listed inTable 1. Further provided herein are methods for reducing colonizationof a subject's anterior nares or nasal cavity by a pathogenicmicroorganism, the method comprising the steps of: administering to asubject having a pathogenic microorganism in the subject's anteriornares or nasal cavity, a live, purified population of bacteria, whereinthe live, purified population of bacteria comprises a plurality ofspecies of Corynebacterium. Further provided herein are methods whereinthe plurality of species of Corynebacterium comprises C. accolens, C.pseudodiphtheriticum, C. amycolatum, C. propinquum, C. glutamicum, or C.striatum. Further provided herein are methods wherein the pathogenicmicroorganism comprises Staphylococcus aureus, Streptococcus pneumoniae,or Pseudomonas aeruginosa. In some embodiments, provided herein aremethods for restoration of a loss of smell, comprising: administering toa subject having an airway inflammatory condition, a live, purifiedpopulation of bacteria, wherein the live, purified population ofbacteria comprises a plurality of species of Corynebacterium.

In some embodiments, provided herein are compositions for the preventionor treatment of neurological conditions. In some embodiments, theneurological condition is one associated with deficit in olfactoryperception. In some embodiments, a subject having the neurologicalcondition is identified as having a deficit in olfactory perception,e.g., marked by a reduction in capacity for smell. Reduction or loss ofsmell is a condition associated with disease onset for a variety ofneurological conditions involving compromised integrity of cellular andmucosal barriers protecting the CNS, in particular in themicroenvironment proximal to the olfactory nerve. In some embodiments,the neurological condition is Parkinson's disease (PD), incidental Lewybody disorder (iLBD), dementia with Lewy bodies (DLB), Alzheimer'sdisease (AD), multiple system atrophy (MSA), progressive supranuclearpalsy (PSP), frontotemporal dementia (FTD), amyotrophic lateralsclerosis (ALS), pure autonomic failure (PAF), schizophrenia,Creutzfeldt-Jakob disease (CJD), autism spectrum disorder (ASD),posttraumatic stress disorder (PTSD), anxiety, or depression. In someembodiments, the ASD is autistic disorder, pervasive developmentaldisorder—not otherwise specified (PDD-NOS), Asperger Syndrome, ChildhoodDisintegrative Disorder (CDD), or Rett Syndrome. In some embodiments,the anxiety is generalized anxiety disorder, obsessive-compulsivedisorder, panic disorder, post-traumatic stress disorder, or socialphobia. In some embodiments, compositions described comprise beneficialbacteria present in an amount sufficient for a reduction in incidence ofcolonization of a pathogenic bacteria. In some embodiments, thecondition relates to a bacterial infection. Sources for bacterialinfections for prevention or treatment with pharmaceutical compositionsdescribed herein include, without limitation, S. aureus(methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S.aureus (MSSA)), S. pneumoniae, Pseudomonas aeruginosa, Bordetellapertussis, and Burkholderia pseudomallei (associated with melioidosis).In some embodiments, a pharmaceutical composition described herein isadministered as treatment for a viral condition, or as an adjuvant to atherapy for treatment of a viral condition. In further embodiments, thevirus is a virus targeting the respiratory tract. Exemplary virusestargeting the respiratory tract include, without limitation, influenza A(e.g., H1N1 and H1N5), influenza B, an adenovirus, respiratory syncytialvirus (RSV), enterovirus (EVs), human rhinovirus (HRV), humanmetapneumovirus (HMPV), human bocavirus (HBoV), coronavirus (CoV) (e.g.,SARS-CoV-2, SARS-CoV Tor2, and MERS-CoV), and parainfluenza virus (PIV).Exemplary therapies for viral conditions include, without limitation,oseltamivir, zanamivir, ribavirin, palivizumab, and aspirin. In someembodiments, a pharmaceutical composition used to treat or prevent aneurological condition described herein comprises at least one species(or strain) listed in Table 1 or Table 2, or a mixture listed in Tables4-7. In some embodiments, a pharmaceutical composition used to treat orprevent a neurological condition described herein comprises a strain ofC. pseudodiphtheriticum and, optionally, a strain of D. pigrum. In someembodiments, a method for treating nasal colonization by at least onepathogenic microorganism in a subject is provided, the method comprisingthe steps of: administering a pharmaceutical composition to the subject,wherein the pharmaceutical composition comprises a Corynebacteriumstrain listed in Table 1, and a Dolosigranulum strain listed in Table 2,or a mixture listed in Tables 4-7. In some embodiments, a method fortreating nasal colonization by at least one pathogenic microorganism ina subject is provided, the method comprising the steps of: administeringa pharmaceutical composition to the subject, wherein the pharmaceuticalcomposition comprises a C. pseudodiphtheriticum strain listed in Table1, and a Dolosigranulum strain listed in Table 2, or a mixture listed inTables 4-7.

In some embodiments, provided herein are pharmaceutical compositions,wherein the pharmaceutical compositions comprise: a live, purifiedpopulation of bacteria, wherein the live, purified population ofbacteria comprises a plurality of strains of Corynebacteriumpseudodiphtheriticum; and a pharmaceutically acceptable excipient.Further provided herein is a pharmaceutical composition, wherein thepharmaceutical composition is formulated for intranasal administration.Further provided herein is a pharmaceutical composition, wherein thepharmaceutical composition is formulated for oral administration.Further provided herein is a pharmaceutical composition, wherein thepharmaceutical composition is in a liquid, solid, semisolid, or aerosoldosage form. Further provided herein is a pharmaceutical composition,wherein the pharmaceutical composition is in a dosage form of asuspension, capsule, gel, tablet, lozenge, pill, or powder. Furtherprovided herein is a pharmaceutical composition, wherein the live,purified population of bacteria is present in a total amount of up to10{circumflex over ( )}15 cfu. Further provided herein is apharmaceutical composition, wherein the wherein the live, purifiedpopulation of bacteria is present in a total amount of at least10{circumflex over ( )}3 cfu. Further provided herein is apharmaceutical composition, wherein the live, purified population ofbacteria is present in a total amount of 10{circumflex over ( )}3 to10{circumflex over ( )}2 cfu. Further provided herein is apharmaceutical composition, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a pharmaceutical composition, wherein thelive, purified population of bacteria comprises up to 10 strains. Insome embodiments, provided herein is a method, comprising administeringto a subject to a subject in need thereof, the pharmaceuticalcomposition described herein, wherein the subject has a respiratorycondition. Further provided herein is a method, wherein the respiratorycondition is asthma, COPD, rhinitis, lung cancer, MRSA, pneumonia(including hospital-acquired pneumonia (HAP), ventilator-associatedpneumonia (VAP), and community acquired pneumonia (CAP)), or cysticfibrosis. In some embodiments, provided herein is use of thepharmaceutical composition described herein in the manufacture of amedicament for the treatment of asthma, COPD, rhinitis, lung cancer,MRSA, (including hospital-acquired pneumonia (HAP),ventilator-associated pneumonia (VAP), and community acquired pneumonia(CAP)), cystic fibrosis, idiopathic pulmonary fibrosis, or interstitiallung disease in a subject. In some embodiments, provided herein is useof the pharmaceutical composition described herein in the manufacture ofa medicament for the treatment of Parkinson's disease (PD), incidentalLewy body disorder (iLBD), dementia with Lewy bodies (DLB), Alzheimer'sdisease (AD), multiple system atrophy (MSA), progressive supranuclearpalsy (PSP), frontotemporal dementia (FTD), amyotrophic lateralsclerosis (ALS), pure autonomic failure (PAF), schizophrenia, orCreutzfeldt-Jakob disease (CJD) in a subject.

In some embodiments, provided herein are pharmaceutical compositions,wherein the pharmaceutical compositions comprise: a live, purifiedpopulation of bacteria, wherein the live, purified population ofbacteria comprises a plurality of species of Corynebacterium; and apharmaceutically acceptable excipient. Further provided herein is apharmaceutical composition, wherein the pharmaceutical composition isformulated for intranasal administration. Further provided herein is apharmaceutical composition, wherein the pharmaceutical composition isformulated for oral administration. Further provided herein is apharmaceutical composition, wherein the pharmaceutical composition is ina liquid, solid, semisolid, or aerosol dosage form. Further providedherein is a pharmaceutical composition, wherein the pharmaceuticalcomposition is in a dosage form of a suspension, capsule, gel, tablet,lozenge, pill, or powder. Further provided herein is a pharmaceuticalcomposition, wherein the live, purified population of bacteria ispresent in a total amount of up to 10{circumflex over ( )}5 cfu. Furtherprovided herein is a pharmaceutical composition, wherein the wherein thelive, purified population of bacteria is present in a total amount of atleast 10{circumflex over ( )}3 cfu. Further provided herein is apharmaceutical composition, wherein the live, purified population ofbacteria is present in a total amount of 10{circumflex over ( )}3 to10{circumflex over ( )}12 cfu. Further provided herein is apharmaceutical composition, wherein the species of Corynebacterium is C.accolens, C. pseudodiphtheriticum, C. propinquum, C. glutamicum, or C.striatum. Further provided herein is a pharmaceutical composition,wherein the species of Corynebacterium is C. accolens, C. afermentans,C. ammoniagenes, C. amycolatum, C. argentoratense, C. aquaticum, C.auris, C. bovis, C. diphtheria, C. equi (now Rhodococcus equi), C.efficiens, C. flavescens, C. glucuronolyticum, C. glutamicum, C.granulosum, C. haemolyticum, C. halofytica, C. kroppenstedtii, C.jeikeium, C. macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. Furtherprovided herein is a pharmaceutical composition, wherein the species ofCorynebacterium is selected from a strain listed in Table 1. Furtherprovided herein is a pharmaceutical composition, wherein the live,purified population of bacteria comprises up to 10 strains. In someembodiments, provided herein is a method, comprising administering to asubject to a subject in need thereof, the pharmaceutical compositiondescribed herein, wherein the subject has a respiratory condition.Further provided herein is a method, wherein the respiratory conditionis asthma, COPD, rhinitis, lung cancer, MRSA, pneumonia (includinghospital-acquired pneumonia (HAP), ventilator-associated pneumonia(VAP), and community acquired pneumonia (CAP)), cystic fibrosis,idiopathic pulmonary fibrosis, or interstitial lung disease. In someembodiments, provided herein is use of the pharmaceutical compositiondescribed herein in the manufacture of a medicament for the treatment ofasthma, COPD, rhinitis, lung cancer, MRSA, (including hospital-acquiredpneumonia (HAP), ventilator-associated pneumonia (VAP), and communityacquired pneumonia (CAP)), cystic fibrosis, idiopathic pulmonaryfibrosis, or interstitial lung disease in a subject. In someembodiments, provided herein is use of the pharmaceutical compositiondescribed herein in the manufacture of a medicament for the treatment ofParkinson's disease (PD), incidental Lewy body disorder (iLBD), dementiawith Lewy bodies (DLB), Alzheimer's disease (AD), multiple systematrophy (MSA), progressive supranuclear palsy (PSP), frontotemporaldementia (FTD), amyotrophic lateral sclerosis (ALS), pure autonomicfailure (PAF), schizophrenia, Creutzfeldt-Jakob disease (CJD), autismspectrum disorder (ASD), posttraumatic stress disorder (PTSD), anxiety,or depression in a subject. In some embodiments, the ASD is autisticdisorder, pervasive developmental disorder—not otherwise specified(PDD-NOS), Asperger Syndrome, Childhood Disintegrative Disorder (CDD),or Rett Syndrome. In some embodiments, the anxiety is generalizedanxiety disorder, obsessive-compulsive disorder, panic disorder,post-traumatic stress disorder, or social phobia.

In some embodiments, provided herein are pharmaceutical compositions,wherein the pharmaceutical compositions comprise: a live, purifiedpopulation of bacteria that comprises: a plurality of strains ofDolosigranulum pigrum; and a pharmaceutically acceptable excipient.Further provided herein is a pharmaceutical composition, wherein thepharmaceutical composition is formulated for intranasal administration.Further provided herein is a pharmaceutical composition, wherein thepharmaceutical composition is formulated for oral administration.Further provided herein is a pharmaceutical composition, wherein thepharmaceutical composition is in a liquid, solid, semisolid, or aerosoldosage form. Further provided herein is a pharmaceutical composition,wherein the pharmaceutical composition is in a dosage form of asuspension, capsule, gel, tablet, lozenge, pill, or powder. Furtherprovided herein is a pharmaceutical composition, wherein the live,purified population of bacteria comprises up to 10 strains. In someembodiments, provided herein is a method, comprising administering to asubject to a subject in need thereof, the pharmaceutical compositiondescribed herein, wherein the subject has a respiratory condition.Further provided herein is a method, wherein the respiratory conditionis asthma, COPD, rhinitis, lung cancer, MRSA, pneumonia (includinghospital-acquired pneumonia (HAP), ventilator-associated pneumonia(VAP), and community acquired pneumonia (CAP)), cystic fibrosis,idiopathic pulmonary fibrosis, or interstitial lung disease. In someembodiments, provided herein is use of the pharmaceutical compositiondescribed herein in the manufacture of a medicament for the treatment ofasthma, COPD, rhinitis, lung cancer, MRSA, pneumonia (includinghospital-acquired pneumonia (HAP), ventilator-associated pneumonia(VAP), and community acquired pneumonia (CAP)), cystic fibrosis,idiopathic pulmonary fibrosis, or interstitial lung disease in asubject. In some embodiments, provided herein is use of thepharmaceutical composition described herein in the manufacture of amedicament for the treatment of Parkinson's disease (PD), incidentalLewy body disorder (iLBD), dementia with Lewy bodies (DLB), Alzheimer'sdisease (AD), multiple system atrophy (MSA), progressive supranuclearpalsy (PSP), frontotemporal dementia (FTD), amyotrophic lateralsclerosis (ALS), pure autonomic failure (PAF), schizophrenia,Creutzfeldt-Jakob disease (CJD), autism spectrum disorder (ASD),posttraumatic stress disorder (PTSD), anxiety, or depression in asubject. In some embodiments, the ASD is autistic disorder, pervasivedevelopmental disorder—not otherwise specified (PDD-NOS), AspergerSyndrome, Childhood Disintegrative Disorder (CDD), or Rett Syndrome. Insome embodiments, the anxiety is generalized anxiety disorder,obsessive-compulsive disorder, panic disorder, post-traumatic stressdisorder, or social phobia.

In some embodiments, provided herein are pharmaceutical compositions,wherein the pharmaceutical compositions comprise: a live, purifiedpopulation of bacteria that comprises: a plurality of strains ofCorynebacterium pseudodiphtheriticum; and at least one strain ofDolosigranulum pigrum; and a pharmaceutically acceptable excipient.Further provided herein is a pharmaceutical composition, wherein thepharmaceutical composition is formulated for intranasal administration.Further provided herein is a pharmaceutical composition, wherein thepharmaceutical composition is formulated for oral administration.Further provided herein is a pharmaceutical composition, wherein thepharmaceutical composition is in a liquid, solid, semisolid, or aerosoldosage form. Further provided herein is a pharmaceutical composition,wherein the pharmaceutical composition is in a dosage form of asuspension, capsule, gel, tablet, lozenge, pill, or powder. Furtherprovided herein is a pharmaceutical composition, wherein the live,purified population of bacteria is present in a total amount of up to10{circumflex over ( )}15 cfu. Further provided herein is apharmaceutical composition, wherein the wherein the live, purifiedpopulation of bacteria is present in a total amount of at least10{circumflex over ( )}3 cfu. Further provided herein is apharmaceutical composition, wherein the live, purified population ofbacteria is present in a total amount of 10{circumflex over ( )}3 to10{circumflex over ( )}2 cfu. Further provided herein is apharmaceutical composition, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a pharmaceutical composition, wherein theDolosigranulum pigrum is selected from a strain listed in Table 2.Further provided herein is a pharmaceutical composition, wherein thestrain of Corynebacterium pseudodiphtheriticum is selected from a strainlisted in Table 1, and wherein the Dolosigranulum pigrum is selectedfrom a strain listed in Table 2. Further provided herein is apharmaceutical composition comprising a mixture listed in Tables 4-7.Further provided herein is a pharmaceutical composition, wherein thelive, purified population of bacteria comprises up to 10 strains. Insome embodiments, provided herein is a method, comprising administeringto a subject to a subject in need thereof, the pharmaceuticalcomposition described herein, wherein the subject has a respiratorycondition. Further provided herein is a method, wherein the respiratorycondition is asthma, COPD, rhinitis, lung cancer, MRSA, pneumonia,cystic fibrosis, idiopathic pulmonary fibrosis, or interstitial lungdisease. In some embodiments, provided herein is use of thepharmaceutical composition described herein in the manufacture of amedicament for the treatment of asthma, COPD, rhinitis, lung cancer,MRSA, pneumonia (including hospital-acquired pneumonia (HAP),ventilator-associated pneumonia (VAP), and community acquired pneumonia(CAP)), cystic fibrosis, idiopathic pulmonary fibrosis, or interstitiallung disease in a subject. In some embodiments, provided herein is useof the pharmaceutical composition described herein in the manufacture ofa medicament for the treatment of Parkinson's disease (PD), incidentalLewy body disorder (iLBD), dementia with Lewy bodies (DLB), Alzheimer'sdisease (AD), multiple system atrophy (MSA), progressive supranuclearpalsy (PSP), frontotemporal dementia (FTD), amyotrophic lateralsclerosis (ALS), pure autonomic failure (PAF), schizophrenia,Creutzfeldt-Jakob disease (CJD), autism, posttraumatic stress disorder(PTSD), anxiety, or depression in a subject. In some embodiments, theASD is autistic disorder, pervasive developmental disorder—not otherwisespecified (PDD-NOS), Asperger Syndrome, Childhood DisintegrativeDisorder (CDD), or Rett Syndrome. In some embodiments, the anxiety isgeneralized anxiety disorder, obsessive-compulsive disorder, panicdisorder, post-traumatic stress disorder, or social phobia.

In some embodiments, provided herein are pharmaceutical compositions,wherein the pharmaceutical compositions comprise: a live, purifiedpopulation of bacteria present in a total amount of at least10{circumflex over ( )}3 cfu, and wherein the live, purified populationof bacteria comprises: a strain of Corynebacterium pseudodiphtheriticum;and a strain of Dolosigranulum pigrum; and a pharmaceutically acceptableexcipient, wherein the pharmaceutical composition is formulated forintranasal administration. Further provided herein is a pharmaceuticalcomposition, wherein the live, purified population of bacteria ispresent in a total amount of up to 10{circumflex over ( )}15 cfu.Further provided herein is a pharmaceutical composition, wherein thelive, purified population of bacteria is present in a total amount of10{circumflex over ( )}3 to 10{circumflex over ( )}2 cfu. Furtherprovided herein is a pharmaceutical composition, wherein the strain ofCorynebacterium pseudodiphtheriticum is selected from a strain listed inTable 1. Further provided herein is a pharmaceutical composition,wherein the Dolosigranulum pigrum is selected from a strain listed inTable 2. Further provided herein is a pharmaceutical composition,wherein the strain of Corynebacterium pseudodiphtheriticum is selectedfrom a strain listed in Table 1, and wherein the Dolosigranulum pigrumis selected from a strain listed in Table 2. Further provided herein isa pharmaceutical composition comprising a mixture listed in Tables 4-7.Further provided herein is a pharmaceutical composition, wherein thelive, purified population of bacteria comprises up to 10 strains. Insome embodiments, provided herein is a method, comprising administeringto a subject to a subject in need thereof, the pharmaceuticalcomposition described herein, wherein the subject has a respiratorycondition. Further provided herein is a method, wherein the respiratorycondition is asthma, COPD, rhinitis, lung cancer, MRSA, pneumonia(including hospital-acquired pneumonia (HAP), ventilator-associatedpneumonia (VAP), and community acquired pneumonia (CAP)), cysticfibrosis, idiopathic pulmonary fibrosis, or interstitial lung disease.In some embodiments, provided herein is use of the pharmaceuticalcomposition described herein in the manufacture of a medicament for thetreatment of asthma, COPD, rhinitis, lung cancer, MRSA, pneumonia(including hospital-acquired pneumonia (HAP), ventilator-associatedpneumonia (VAP), and community acquired pneumonia (CAP)), or cysticfibrosis, idiopathic pulmonary fibrosis, or interstitial lung disease ina subject. In some embodiments, provided herein is use of thepharmaceutical composition described herein in the manufacture of amedicament for the treatment of Parkinson's disease (PD), incidentalLewy body disorder (iLBD), dementia with Lewy bodies (DLB), Alzheimer'sdisease (AD), multiple system atrophy (MSA), progressive supranuclearpalsy (PSP), frontotemporal dementia (FTD), amyotrophic lateralsclerosis (ALS), pure autonomic failure (PAF), schizophrenia, orCreutzfeldt-Jakob disease (CJD) in a subject.

In some embodiments, provided herein is are pharmaceutical compositions,wherein the pharmaceutical compositions comprise: a live, purifiedpopulation of bacteria present in a total amount of at least10{circumflex over ( )}3 cfu, and wherein the live, purified populationof bacteria comprises: a strain of Corynebacterium pseudodiphtheriticum;and a strain of Dolosigranulum pigrum; and a pharmaceutically acceptableexcipient, wherein the pharmaceutical composition is formulated for oraladministration. Further provided herein is a pharmaceutical composition,wherein the live, purified population of bacteria is present in a totalamount of up to 10{circumflex over ( )}15 cfu. Further provided hereinis a pharmaceutical composition, wherein the wherein the live, purifiedpopulation of bacteria is present in a total amount of at least10{circumflex over ( )}3 cfu. Further provided herein is apharmaceutical composition, wherein the live, purified population ofbacteria is present in a total amount of 10{circumflex over ( )}3 to10{circumflex over ( )}2 cfu. Further provided herein is apharmaceutical composition, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a pharmaceutical composition, wherein theDolosigranulum pigrum is selected from a strain listed in Table 2.Further provided herein is a pharmaceutical composition, wherein thestrain of Corynebacterium pseudodiphtheriticum is selected from a strainlisted in Table 1, and wherein the Dolosigranulum pigrum is selectedfrom a strain listed in Table 2. Further provided herein is apharmaceutical composition comprising a mixture listed in Tables 4-7.Further provided herein is a pharmaceutical composition, wherein thelive, purified population of bacteria comprises up to 10 strains. Insome embodiments, provided herein is a method, comprising administeringto a subject to a subject in need thereof, the pharmaceuticalcomposition described herein, wherein the subject has a respiratorycondition. Further provided herein is a method, wherein the respiratorycondition is asthma, COPD, rhinitis, lung cancer, MRSA, pneumonia(including hospital-acquired pneumonia (HAP), ventilator-associatedpneumonia (VAP), and community acquired pneumonia (CAP)), cysticfibrosis, idiopathic pulmonary fibrosis, or interstitial lung disease.In some embodiments, provided herein is use of the pharmaceuticalcomposition described herein in the manufacture of a medicament for thetreatment of asthma, COPD, rhinitis, lung cancer, MRSA, pneumonia(including hospital-acquired pneumonia (HAP), ventilator-associatedpneumonia (VAP), and community acquired pneumonia (CAP)), or cysticfibrosis, idiopathic pulmonary fibrosis, or interstitial lung disease ina subject. In some embodiments, provided herein is use of thepharmaceutical composition described herein in the manufacture of amedicament for the treatment of Parkinson's disease (PD), incidentalLewy body disorder (iLBD), dementia with Lewy bodies (DLB), Alzheimer'sdisease (AD), multiple system atrophy (MSA), progressive supranuclearpalsy (PSP), frontotemporal dementia (FTD), amyotrophic lateralsclerosis (ALS), pure autonomic failure (PAF), schizophrenia,Creutzfeldt-Jakob disease (CJD), autism spectrum disorder (ASD),posttraumatic stress disorder (PTSD), anxiety, or depression. In someembodiments, the ASD is autistic disorder, pervasive developmentaldisorder—not otherwise specified (PDD-NOS), Asperger Syndrome, ChildhoodDisintegrative Disorder (CDD), or Rett Syndrome. In some embodiments,the anxiety is generalized anxiety disorder, obsessive-compulsivedisorder, panic disorder, post-traumatic stress disorder, or socialphobia.

In some embodiments, provided herein are methods for microbiomemodification in a subject, comprising administering to a subject in needthereof. a population of purified, live bacteria comprising at least onestrain of bacteria present in an amount sufficient for prevention ortreatment of a lung condition, wherein the at least one strain ofbacteria is isolated from upper respiratory tract of a donor. In someembodiments, provided herein are methods for treatment of aninflammatory lung condition, comprising administering to a subjecthaving an inflammatory lung condition: a population of purified, livebacteria comprising at least one strain of bacteria present in an amountsufficient for reduction in incidence of colonization of a pathogenicbacterium in the nasal cavity, wherein the at least one strain ofbacteria is isolated from upper respiratory tract of a donor. Furtherprovided herein are methods, wherein the pathogenic bacterium comprisesStaphylococcus aureus, Streptococcus pneumoniae, or Pseudomonasaeruginosa. Further provided herein are methods, wherein the pathogenicbacterium a strain listed Table 3. In some embodiments, provided hereinare methods for treatment of an airway inflammatory condition,comprising: administering to a subject in need thereof, a live, purifiedpopulation of bacteria, wherein the live, purified population ofbacteria comprises: a plurality of strains of Corynebacteriumpseudodiphtheriticum; and at least one strain of Dolosigranulum pigrum.Further provided herein is a method, wherein the strain ofCorynebacterium pseudodiphtheriticum is selected from a strain listed inTable 1. Further provided herein is a method, wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a pharmaceutical composition comprising a mixture listed inTables 4-7. Further provided herein is a method, wherein the strain ofCorynebacterium pseudodiphtheriticum is selected from a strain listed inTable 1, and wherein the Dolosigranulum pigrum is selected from a strainlisted in Table 2. Further provided herein is a method, wherein theairway inflammatory condition is asthma, COPD, rhinitis, MRSA, pneumonia(including hospital-acquired pneumonia (HAP), ventilator-associatedpneumonia (VAP), and community acquired pneumonia (CAP)), cysticfibrosis, idiopathic pulmonary fibrosis, or interstitial lung disease.Further provided herein is a method, wherein the bacterial population isadministered intranasally. Further provided herein is a method, whereinthe bacterial population is administered orally. Further provided hereinis a method, wherein the subject is an infant. Further provided hereinis a method, wherein the subject is a child. Further provided herein isa method, wherein the subject is an adult. Further provided herein aremethods, wherein the live, purified population of bacteria is present ina total amount of up to 10{circumflex over ( )}5 cfu. Further providedherein are methods, wherein the live, purified population of bacteria ispresent in a total amount of 10{circumflex over ( )}3 to 10{circumflexover ( )}12 cfu.

In some embodiments, provided herein are methods for treatment of alower respiratory tract condition, comprising: administering to asubject having a lower respiratory tract infection, a live, purifiedpopulation of bacteria, wherein the live, purified population ofbacteria comprises: a strain of Corynebacterium pseudodiphtheriticum;and a strain of Dolosigranulum pigrum. In some embodiments, providedherein is a method for treating an airway inflammatory condition,comprising: administering to a subject in need thereof, a live, purifiedpopulation of bacteria, wherein the live, purified population ofbacteria comprises: a plurality of strains of Corynebacteriumpseudodiphtheriticum; and at least one strain of Dolosigranulum pigrum.Further provided herein is a method, wherein the strain ofCorynebacterium pseudodiphtheriticum is selected from a strain listed inTable 1. Further provided herein is a method, wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a method, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1, andwherein the Dolosigranulum pigrum is selected from a strain listed inTable 2. Further provided herein is a pharmaceutical compositioncomprising a mixture listed in Tables 4-7. Further provided herein is amethod, wherein the airway inflammatory condition is asthma, COPD,rhinitis, MRSA, pneumonia (including hospital-acquired pneumonia (HAP),ventilator-associated pneumonia (VAP), and community acquired pneumonia(CAP)), cystic fibrosis, idiopathic pulmonary fibrosis, or interstitiallung disease. Further provided herein is a method, wherein the live,purified population of bacteria is administered intranasally. Furtherprovided herein is a method, wherein the live, purified population ofbacteria is administered orally. Further provided herein is a method,wherein the subject is an infant. Further provided herein is a method,wherein the subject is a child. Further provided herein is a method,wherein the subject is an adult. Further provided herein are methods,wherein the live, purified population of bacteria is present in a totalamount of up to 10{circumflex over ( )}5 cfu. Further provided hereinare methods, wherein the live, purified population of bacteria ispresent in a total amount of 10{circumflex over ( )}3 to 10{circumflexover ( )}12 cfu.

In some embodiments, provided herein are methods for treatment of anairway inflammatory condition, comprising: administering to a subjecthaving an airway inflammatory condition, a live, purified population ofbacteria, wherein the live, purified population of bacteria comprises aplurality of species of Corynebacterium. Further provided herein is amethod, wherein the species of Corynebacterium is C. accolens, C.afermentans, C. ammoniagenes, C. amycolatum, C. argentoratense, C.aquaticum, C. auris, C. bovis, C. diphtheria, C. equi (now Rhodococcusequi), C. efficiens, C. flavescens, C. glucuronolyticum, C. glutamicum,C. granulosum, C. haemolyticum, C. halofytica, C. kroppenstedtii, C.jeikeium, C. macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. In someembodiments, provided herein is a method for treating an airwayinflammatory condition, comprising: administering to a subject in needthereof, a live, purified population of bacteria, wherein the live,purified population of bacteria comprises: a plurality of strains ofCorynebacterium pseudodiphtheriticum; and at least one strain ofDolosigranulum pigrum. Further provided herein is a method, wherein thestrain of Corynebacterium pseudodiphtheriticum is selected from a strainlisted in Table 1. Further provided herein is a method, wherein theDolosigranulum pigrum is selected from a strain listed in Table 2.Further provided herein is a method, wherein the strain ofCorynebacterium pseudodiphtheriticum is selected from a strain listed inTable 1, and wherein the Dolosigranulum pigrum is selected from a strainlisted in Table 2. Further provided herein is a pharmaceuticalcomposition comprising a mixture listed in Tables 4-7. Further providedherein is a method, wherein the airway inflammatory condition is asthma,COPD, rhinitis, MRSA, pneumonia (including hospital-acquired pneumonia(HAP), ventilator-associated pneumonia (VAP), and community acquiredpneumonia (CAP)), cystic fibrosis, idiopathic pulmonary fibrosis, orinterstitial lung disease. Further provided herein is a method, whereinthe live, purified population of bacteria is administered intranasally.Further provided herein is a method, wherein the live, purifiedpopulation of bacteria is administered orally. Further provided hereinis a method, wherein the subject is an infant. Further provided hereinis a method, wherein the subject is a child. Further provided herein isa method, wherein the subject is an adult. Further provided herein aremethods, wherein the live, purified population of bacteria is present ina total amount of up to 10{circumflex over ( )}15 cfu. Further providedherein are methods, wherein the live, purified population of bacteria ispresent in a total amount of 10{circumflex over ( )}3 to 10{circumflexover ( )}12 cfu.

In some embodiments, provided herein are methods for treatment of anairway inflammatory condition, comprising: administering to a subjecthaving an airway inflammatory condition, a live, purified population ofbacteria, wherein the live, purified population of bacteria comprises: aplurality of strains of Dolosigranulum pigrum. In some embodiments,provided herein is a method for treating an airway inflammatorycondition, comprising: administering to a subject in need thereof, alive, purified population of bacteria, wherein the live, purifiedpopulation of bacteria comprises: a plurality of strains ofCorynebacterium pseudodiphtheriticum; and at least one strain ofDolosigranulum pigrum. Further provided herein is a method, wherein thestrain of Corynebacterium pseudodiphtheriticum is selected from a strainlisted in Table 1. Further provided herein is a method, wherein theDolosigranulum pigrum is selected from a strain listed in Table 2.Further provided herein is a method, wherein the strain ofCorynebacterium pseudodiphtheriticum is selected from a strain listed inTable 1, and wherein the Dolosigranulum pigrum is selected from a strainlisted in Table 2. Further provided herein is a method, wherein theairway inflammatory condition is asthma, COPD, rhinitis, MRSA, pneumonia(including hospital-acquired pneumonia (HAP), ventilator-associatedpneumonia (VAP), and community acquired pneumonia (CAP)), cysticfibrosis, idiopathic pulmonary fibrosis, or interstitial lung disease.Further provided herein is a method, wherein the live, purifiedpopulation of bacteria is administered intranasally. Further providedherein is a method, wherein the live, purified population of bacteria isadministered orally. Further provided herein is a method, wherein thesubject is an infant. Further provided herein is a method, wherein thesubject is a child. Further provided herein is a method, wherein thesubject is an adult. Further provided herein are methods, wherein thelive, purified population of bacteria is present in a total amount of upto 10{circumflex over ( )}15 cfu. Further provided herein are methods,wherein the live, purified population of bacteria is present in a totalamount of 10{circumflex over ( )}3 to 10{circumflex over ( )}12 cfu.

In some embodiments, provided herein are methods for treatment of lungcancer, comprising: administering to a subject having lung cancer alive, purified population of bacteria, wherein the live, purifiedpopulation of bacteria comprises: at least one species ofCorynebacterium, optionally at least one strain of Corynebacteriumpseudodiphtheriticum; and optionally, at least one strain ofDolosigranulum pigrum. Further provided herein is a method, wherein thespecies of Corynebacterium is C. accolens, C. afermentans, C.ammoniagenes, C. amycolatum, C. argentoratense, C. aquaticum, C. auris,C. bovis, C. diphtheria, C. equi (now Rhodococcus equi), C. efficiens,C. flavescens, C. glucuronolyticum, C. glutamicum, C. granulosum, C.haemolyticum, C. halofytica, C. kroppenstedtii, C. jeikeium, C.macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. Furtherprovided herein is a method, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a method, wherein the Dolosigranulum pigrumis selected from a strain listed in Table 2. Further provided herein isa method, wherein the strain of Corynebacterium pseudodiphtheriticum isselected from a strain listed in Table 1, and wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a pharmaceutical composition comprising a mixture listed inTables 4-7. Further provided herein is a method, wherein the live,purified population of bacteria is administered intranasally. Furtherprovided herein is a method, wherein the live, purified population ofbacteria is administered orally. Further provided herein is a method,wherein the subject is an infant. Further provided herein is a method,wherein the subject is a child. Further provided herein is a method,wherein the subject is an adult. Further provided herein are methods,wherein the live, purified population of bacteria is present in a totalamount of up to 10{circumflex over ( )}5 cfu. Further provided hereinare methods, wherein the live, purified population of bacteria ispresent in a total amount of 10{circumflex over ( )}3 to 10{circumflexover ( )}12 cfu.

In some embodiments, provided herein are methods for treatment ofcancer, comprising: administering to a subject having cancer, a live,purified population of bacteria as an adjuvant therapy, wherein thelive, purified population of bacteria comprises: at least one species ofCorynebacterium, optionally at least one strain of Corynebacteriumpseudodiphtheriticum; and optionally, at least one strain ofDolosigranulum pigrum. Further provided herein is a method, wherein thespecies of Corynebacterium is C. accolens, C. afermentans, C.ammoniagenes, C. amycolatum, C. argentoratense, C. aquaticum, C. auris,C. bovis, C. diphtheria, C. equi (now Rhodococcus equi), C. efficiens,C. flavescens, C. glucuronolyticum, C. glutamicum, C. granulosum, C.haemolyticum, C. halofytica, C. kroppenstedtii, C. jeikeium, C.macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. Furtherprovided herein is a method, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a method, wherein the Dolosigranulum pigrumis selected from a strain listed in Table 2. Further provided herein isa method, wherein the strain of Corynebacterium pseudodiphtheriticum isselected from a strain listed in Table 1, and wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a pharmaceutical composition comprising a mixture listed inTables 4-7. Further provided herein is a method, wherein the cancer is asolid cancer or a hematopoietic cancer. Further provided herein is amethod, wherein the solid cancer is a carcinoma or a sarcoma. Furtherprovided herein is a method, wherein the hematopoietic cancer is aleukemia, myeloma or lymphoma. Further provided herein is a method,wherein the adjuvant therapy is chemotherapy, radiation therapy, orcheckpoint inhibitor therapy. Further provided herein is a method,wherein the live, purified population of bacteria is administered beforeor after administration of the chemotherapy, radiation therapy, orcheckpoint inhibitor therapy. Further provided herein is a method,wherein the live, purified population of bacteria is administeredintranasally. Further provided herein is a method, wherein the live,purified population of bacteria is administered orally. Further providedherein is a method, wherein the subject is an infant. Further providedherein is a method, wherein the subject is a child. Further providedherein is a method, wherein the subject is an adult. Further providedherein are methods, wherein the live, purified population of bacteria ispresent in a total amount of up to 10{circumflex over ( )}15 cfu.Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is present in a total amount of 10{circumflexover ( )}3 to 10{circumflex over ( )}12 cfu.

In some embodiments, provided herein are methods for treatment ofasthma, comprising: administering to a subject having asthma a live,purified population of bacteria, wherein the live, purified populationof bacteria comprises: at least one species of Corynebacterium,optionally at least one strain of Corynebacterium pseudodiphtheriticum;and optionally, at least one strain of Dolosigranulum pigrum. Furtherprovided herein is a method, wherein the species of Corynebacterium isC. accolens, C. afermentans, C. ammoniagenes, C. amycolatum, C.argentoratense, C. aquaticum, C. auris, C. bovis, C. diphtheria, C. equi(now Rhodococcus equi), C. efficiens, C. flavescens, C.glucuronolyticum, C. glutamicum, C. granulosum, C. haemolyticum, C.halofytica, C. kroppenstedtii, C. jeikeium, C. macginleyi, C.matruchotii, C. minutissimum, C. parvum (Propionibacterium acnes), C.paurometabolum, C. propinquum, C. pseudodiphtheriticum (C. hofmannii),C. pseudotuberculosis, C. ovis, C. pyogenes—Trueperella pyogenes, C.urealyticum, C. renale, C. spec, C. striatum, C. tenuis, C. ulcerans, C.urealyticum, or C. xerosis. Further provided herein is a method, whereinthe strain of Corynebacterium pseudodiphtheriticum is selected from astrain listed in Table 1. Further provided herein is a method, whereinthe Dolosigranulum pigrum is selected from a strain listed in Table 2.Further provided herein is a method, wherein the strain ofCorynebacterium pseudodiphtheriticum is selected from a strain listed inTable 1, and wherein the Dolosigranulum pigrum is selected from a strainlisted in Table 2. Further provided herein is a pharmaceuticalcomposition comprising a mixture listed in Tables 4-7. Further providedherein is a method, wherein the live, purified population of bacteria isadministered intranasally. Further provided herein is a method, whereinthe live, purified population of bacteria is administered orally.Further provided herein is a method, wherein the subject is an infant.Further provided herein is a method, wherein the subject is a child.Further provided herein is a method, wherein the subject is an adult.Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is present in a total amount of up to10{circumflex over ( )}5 cfu. Further provided herein are methods,wherein the live, purified population of bacteria is present in a totalamount of 10{circumflex over ( )}3 to 10{circumflex over ( )}12 cfu.

In some embodiments, provided herein are methods for treatment of aviral infection condition, comprising: administering to a subject havinga viral infection a live, purified population of bacteria, wherein thelive, purified population of bacteria comprises: at least one species ofCorynebacterium, optionally at least one strain of Corynebacteriumpseudodiphtheriticum; and optionally, at least one strain ofDolosigranulum pigrum. Further provided herein is a method, wherein thespecies of Corynebacterium is C. accolens, C. afermentans, C.ammoniagenes, C. amycolatum, C. argentoratense, C. aquaticum, C. auris,C. bovis, C. diphtheria, C. equi (now Rhodococcus equi), C. efficiens,C. flavescens, C. glucuronolyticum, C. glutamicum, C. granulosum, C.haemolyticum, C. halofytica, C. kroppenstedtii, C. jeikeium, C.macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. Furtherprovided herein is a method, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a method, wherein the Dolosigranulum pigrumis selected from a strain listed in Table 2. Further provided herein isa method, wherein the strain of Corynebacterium pseudodiphtheriticum isselected from a strain listed in Table 1, and wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a pharmaceutical composition comprising a mixture listed inTables 4-7. Further provided herein is a method, wherein the viralinfection is influenza A, influenza B, an adenovirus, respiratorysyncytial virus (RSV), enterovirus (EVs), human rhinovirus (HRV), humanmetapneumovirus (HMPV), human bocavirus (HBoV), coronavirus (CoV), orparainfluenza virus (PIV). Further provided herein is a method, whereinthe live, purified population of bacteria is administered intranasally.Further provided herein is a method, wherein the live, purifiedpopulation of bacteria is administered orally. Further provided hereinis a method, wherein the subject is an infant. Further provided hereinis a method, wherein the subject is a child. Further provided herein isa method, wherein the subject is an adult. Further provided herein aremethods, wherein the live, purified population of bacteria is present ina total amount of up to 10{circumflex over ( )}15 cfu. Further providedherein are methods, wherein the live, purified population of bacteria ispresent in a total amount of 10{circumflex over ( )}3 to 10{circumflexover ( )}12 cfu.

In some embodiments, provided herein are methods for treatment ofidiopathic pulmonary fibrosis, comprising: administering to a subjecthaving idiopathic pulmonary fibrosis a live, purified population ofbacteria, wherein the live, purified population of bacteria comprises:at least one species of Corynebacterium, optionally at least one strainof Corynebacterium pseudodiphtheriticum; and optionally, at least onestrain of Dolosigranulum pigrum. Further provided herein is a method,wherein the species of Corynebacterium is C. accolens, C. afermentans,C. ammoniagenes, C. amycolatum, C. argentoratense, C. aquaticum, C.auris, C. bovis, C. diphtheria, C. equi (now Rhodococcus equi), C.efficiens, C. flavescens, C. glucuronolyticum, C. glutamicum, C.granulosum, C. haemolyticum, C. halofytica, C. kroppenstedtii, C.jeikeium, C. macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. Furtherprovided herein is a method, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a method, wherein the Dolosigranulum pigrumis selected from a strain listed in Table 2. Further provided herein isa method, wherein the strain of Corynebacterium pseudodiphtheriticum isselected from a strain listed in Table 1, and wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a pharmaceutical composition comprising a mixture listed inTables 4-7. Further provided herein is a method, wherein the bacterialpopulation is administered intranasally. Further provided herein is amethod, wherein the live, purified population of bacteria isadministered orally. Further provided herein is a method, wherein thesubject is an infant. Further provided herein is a method, wherein thesubject is a child. Further provided herein is a method, wherein thesubject is an adult. Further provided herein are methods, wherein thelive, purified population of bacteria is present in a total amount of upto 10{circumflex over ( )}15 cfu. Further provided herein are methods,wherein the live, purified population of bacteria is present in a totalamount of 10{circumflex over ( )}3 to 10{circumflex over ( )}12 cfu.

In some embodiments, provided herein are methods for treatment of MRSA,comprising: intranasally or orally administering to a subject havingMRSA (MRSA-positive) a live, purified population of bacteria, whereinthe live, purified population of bacteria comprises: at least onespecies of Corynebacterium, optionally at least one strain ofCorynebacterium pseudodiphtheriticum; and at least one strain ofDolosigranulum pigrum. Further provided herein is a method, wherein thespecies of Corynebacterium is C. accolens, C. afermentans, C.ammoniagenes, C. amycolatum, C. argentoratense, C. aquaticum, C. auris,C. bovis, C. diphtheria, C. equi (now Rhodococcus equi), C. efficiens,C. flavescens, C. glucuronolyticum, C. glutamicum, C. granulosum, C.haemolyticum, C. halofytica, C. kroppenstedtii, C. jeikeium, C.macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. Furtherprovided herein is a method, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a method, wherein the Dolosigranulum pigrumis selected from a strain listed in Table 2. Further provided herein isa method, wherein the strain of Corynebacterium pseudodiphtheriticum isselected from a strain listed in Table 1, and wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a pharmaceutical composition comprising a mixture listed inTables 4-7. Further provided herein is a method, wherein the subject isan infant. Further provided herein is a method, wherein the subject is achild. Further provided herein is a method, wherein the subject is anadult. Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is present in a total amount of up to10{circumflex over ( )}15 cfu. Further provided herein are methods,wherein the live, purified population of bacteria is present in a totalamount of 10{circumflex over ( )}3 to 10{circumflex over ( )}12 cfu.

In some embodiments, provided herein are methods for treatment of MSSA,comprising: intranasally or orally administering to a subject havingMSAA (MSSA-positive) a live, purified population of bacteria, whereinthe live, purified population of bacteria comprises: at least onespecies of Corynebacterium, optionally at least one strain ofCorynebacterium pseudodiphtheriticum; and at least one strain ofDolosigranulum pigrum. Further provided herein is a method, wherein thespecies of Corynebacterium is C. accolens, C. afermentans, C.ammoniagenes, C. amycolatum, C. argentoratense, C. aquaticum, C. auris,C. bovis, C. diphtheria, C. equi (now Rhodococcus equi), C. efficiens,C. flavescens, C. glucuronolyticum, C. glutamicum, C. granulosum, C.haemolyticum, C. halofytica, C. kroppenstedtii, C. jeikeium, C.macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. Furtherprovided herein is a method, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a method, wherein the Dolosigranulum pigrumis selected from a strain listed in Table 2. Further provided herein isa method, wherein the strain of Corynebacterium pseudodiphtheriticum isselected from a strain listed in Table 1, and wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a pharmaceutical composition comprising a mixture listed inTables 4-7. Further provided herein is a method, wherein the subject isan infant. Further provided herein is a method, wherein the subject is achild. Further provided herein is a method, wherein the subject is anadult. Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is present in a total amount of up to10{circumflex over ( )}15 cfu. Further provided herein are methods,wherein the live, purified population of bacteria is present in a totalamount of 10{circumflex over ( )}3 to 10{circumflex over ( )}12 cfu.

In some embodiments, provided herein are methods for treatment ofpneumonia, comprising: intranasally or orally administering to a subjecthaving pneumonia a live, purified population of bacteria present in anamount of at least 10{circumflex over ( )}3 cfu, wherein the live,purified population of bacteria comprises: at least one species ofCorynebacterium, optionally at least one strain of Corynebacteriumpseudodiphtheriticum; and at least one strain of Dolosigranulum pigrum.Further provided herein is a method, wherein the species ofCorynebacterium is C. accolens, C. afermentans, C. ammoniagenes, C.amycolatum, C. argentoratense, C. aquaticum, C. auris, C. bovis, C.diphtheria, C. equi (now Rhodococcus equi), C. efficiens, C. flavescens,C. glucuronolyticum, C. glutamicum, C. granulosum, C. haemolyticum, C.halofytica, C. kroppenstedtii, C. jeikeium, C. macginleyi, C.matruchotii, C. minutissimum, C. parvum (Propionibacterium acnes), C.paurometabolum, C. propinquum, C. pseudodiphtheriticum (C. hofmannii),C. pseudotuberculosis, C. ovis, C. pyogenes—Trueperella pyogenes, C.urealyticum, C. renale, C. spec, C. striatum, C. tenuis, C. ulcerans, C.urealyticum, or C. xerosis. Further provided herein is a method, whereinthe strain of Corynebacterium pseudodiphtheriticum is selected from astrain listed in Table 1. Further provided herein is a method, whereinthe Dolosigranulum pigrum is selected from a strain listed in Table 2.Further provided herein is a method, wherein the strain ofCorynebacterium pseudodiphtheriticum is selected from a strain listed inTable 1, and wherein the Dolosigranulum pigrum is selected from a strainlisted in Table 2. Further provided herein is a pharmaceuticalcomposition comprising a mixture listed in Tables 4-7. Further providedherein is a method, wherein the subject is an infant. Further providedherein is a method, wherein the subject is a child. Further providedherein is a method, wherein the subject is an adult. Further providedherein are methods, wherein the live, purified population of bacteria ispresent in a total amount of up to 10{circumflex over ( )}5 cfu. Furtherprovided herein are methods, wherein the live, purified population ofbacteria is present in a total amount of 10{circumflex over ( )}3 to10{circumflex over ( )}12 cfu. Further provided herein are methodswherein the pneumonia is pneumonia is hospital-acquired pneumonia (HAP),ventilator-associated pneumonia (VAP), or community acquired pneumonia(CAP).

In some embodiments, provided herein are methods for treatment ofrhinitis, comprising: administering to a subject having rhinitis a live,purified population of bacteria, wherein the live, purified populationof bacteria comprises: at least one species of Corynebacterium,optionally at least one strain of Corynebacterium pseudodiphtheriticum;and optionally, at least one strain of Dolosigranulum pigrum. Furtherprovided herein is a method, wherein the rhinitis is allergic rhinitisor non-allergic rhinitis. Further provided herein is a method, whereinthe species of Corynebacterium is C. accolens, C. afermentans, C.ammoniagenes, C. amycolatum, C. argentoratense, C. aquaticum, C. auris,C. bovis, C. diphtheria, C. equi (now Rhodococcus equi), C. efficiens,C. flavescens, C. glucuronolyticum, C. glutamicum, C. granulosum, C.haemolyticum, C. halofytica, C. kroppenstedtii, C. jeikeium, C.macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. Furtherprovided herein is a method, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a method, wherein the Dolosigranulum pigrumis selected from a strain listed in Table 2. Further provided herein isa method, wherein the strain of Corynebacterium pseudodiphtheriticum isselected from a strain listed in Table 1, and wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a pharmaceutical composition comprising a mixture listed inTables 4-7. Further provided herein is a method, wherein the bacterialpopulation is administered intranasally. Further provided herein is amethod, wherein the live, purified population of bacteria isadministered orally. Further provided herein is a method, wherein thesubject is an infant. Further provided herein is a method, wherein thesubject is a child. Further provided herein is a method, wherein thesubject is an adult. Further provided herein are methods, wherein thelive, purified population of bacteria is present in a total amount of upto 10{circumflex over ( )}5 cfu. Further provided herein are methods,wherein the live, purified population of bacteria is present in a totalamount of 10{circumflex over ( )}3 to 10{circumflex over ( )}12 cfu.

In some embodiments, provided herein are methods for treatment of COPD,comprising: administering to a subject having COPD a live, purifiedpopulation of bacteria, wherein the live, purified population ofbacteria comprises: at least one species of Corynebacterium, optionallyat least one strain of Corynebacterium pseudodiphtheriticum; andoptionally, at least one strain of Dolosigranulum pigrum. Furtherprovided herein is a method, wherein the species of Corynebacterium isC. accolens, C. afermentans, C. ammoniagenes, C. amycolatum, C.argentoratense, C. aquaticum, C. auris, C. bovis, C. diphtheria, C. equi(now Rhodococcus equi), C. efficiens, C. flavescens, C.glucuronolyticum, C. glutamicum, C. granulosum, C. haemolyticum, C.halofytica, C. kroppenstedtii, C. jeikeium, C. macginleyi, C.matruchotii, C. minutissimum, C. parvum (Propionibacterium acnes), C.paurometabolum, C. propinquum, C. pseudodiphtheriticum (C. hofmannii),C. pseudotuberculosis, C. ovis, C. pyogenes—Trueperella pyogenes, C.urealyticum, C. renale, C. spec, C. striatum, C. tenuis, C. ulcerans, C.urealyticum, or C. xerosis. Further provided herein is a method, whereinthe strain of Corynebacterium pseudodiphtheriticum is selected from astrain listed in Table 1. Further provided herein is a method, whereinthe Dolosigranulum pigrum is selected from a strain listed in Table 2.Further provided herein is a method, wherein the strain ofCorynebacterium pseudodiphtheriticum is selected from a strain listed inTable 1, and wherein the Dolosigranulum pigrum is selected from a strainlisted in Table 2. Further provided herein is a pharmaceuticalcomposition comprising a mixture listed in Tables 4-7. Further providedherein is a method, wherein the bacterial population is administeredintranasally. Further provided herein is a method, wherein the live,purified population of bacteria is administered orally. Further providedherein is a method, wherein the subject is an infant. Further providedherein is a method, wherein the subject is a child. Further providedherein is a method, wherein the subject is an adult. Further providedherein are methods, wherein the live, purified population of bacteria ispresent in a total amount of up to 10{circumflex over ( )}5 cfu. Furtherprovided herein are methods, wherein the live, purified population ofbacteria is present in a total amount of 10{circumflex over ( )}3 to10{circumflex over ( )}12 cfu.

In some embodiments, provided herein are methods for treatment of cysticfibrosis, comprising: administering to a subject having cystic fibrosisa live, purified population of bacteria, wherein the live, purifiedpopulation of bacteria comprises: at least one species ofCorynebacterium, optionally at least one strain of Corynebacteriumpseudodiphtheriticum; and optionally, at least one strain ofDolosigranulum pigrum. Further provided herein is a method, wherein thespecies of Corynebacterium is C. accolens, C. afermentans, C.ammoniagenes, C. amycolatum, C. argentoratense, C. aquaticum, C. auris,C. bovis, C. diphtheria, C. equi (now Rhodococcus equi), C. efficiens,C. flavescens, C. glucuronolyticum, C. glutamicum, C. granulosum, C.haemolyticum, C. halofytica, C. kroppenstedtii, C. jeikeium, C.macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. Furtherprovided herein is a method, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a method, wherein the Dolosigranulum pigrumis selected from a strain listed in Table 2. Further provided herein isa method, wherein the strain of Corynebacterium pseudodiphtheriticum isselected from a strain listed in Table 1, and wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a pharmaceutical composition comprising a mixture listed inTables 4-7. Further provided herein is a method, wherein the bacterialpopulation is administered intranasally. Further provided herein is amethod, wherein the live, purified population of bacteria isadministered orally. Further provided herein is a method, wherein thesubject is an infant. Further provided herein is a method, wherein thesubject is a child. Further provided herein is a method, wherein thesubject is an adult. Further provided herein are methods, wherein thelive, purified population of bacteria is present in a total amount of upto 10{circumflex over ( )}5 cfu. Further provided herein are methods,wherein the live, purified population of bacteria is present in a totalamount of 10{circumflex over ( )}3 to 10{circumflex over ( )}12 cfu.

In some embodiments, provided herein are kits, wherein the kitcomprises: a first container, wherein the first container compriseslive, purified, and lyophilized population of bacteria that comprises: aplurality of strains of Corynebacterium pseudodiphtheriticum; and asecond container, wherein the second container comprises apharmaceutically acceptable excipient. Further provided herein is akite, wherein the strain of Corynebacterium pseudodiphtheriticum isselected from a strain listed in Table 1. Further provided herein arekits, wherein the live, purified, and lyophilized population of bacteriais present in an amount sufficient for treatment of a respiratorycondition. Further provided herein are kits, wherein the live, purified,and lyophilized population of bacteria is present in a total amount ofup to 10{circumflex over ( )}5 cfu. Further provided herein are kits,wherein the live, purified, and lyophilized population of bacteria ispresent in a total amount of 10{circumflex over ( )}3 to 10{circumflexover ( )}12 cfu.

In some embodiments, provided herein are kits, wherein the kitcomprises: a first container, wherein the first container compriseslive, purified, and lyophilized population of bacteria that comprises: aplurality of species of Corynebacterium; and a second container, whereinthe second container comprises a pharmaceutically acceptable excipient.Further provided herein is a kit, wherein the species of Corynebacteriumis selected from a strain listed in Table 1. Further provided herein arekits, wherein the live, purified, and lyophilized population of bacteriais present in an amount sufficient for treatment of a respiratorycondition. Further provided herein are kits, wherein the live, purified,and lyophilized population of bacteria is present in a total amount ofup to 10{circumflex over ( )}5 cfu. Further provided herein are kits,wherein the live, purified, and lyophilized population of bacteria ispresent in a total amount of 10{circumflex over ( )}3 to 10{circumflexover ( )}12 cfu.

In some embodiments, provided herein are kits, wherein the kitcomprises: a first container, wherein the first container compriseslive, purified, and lyophilized population of bacteria that comprises: aplurality of strains of Dolosigranulum pigrum; and a second container,wherein the second container comprises a pharmaceutically acceptableexcipient. Further provided herein is a kit, wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein are kits, wherein the live, purified, and lyophilized populationof bacteria is present in an amount sufficient for treatment of arespiratory condition. Further provided herein are kits, wherein thelive, purified, and lyophilized population of bacteria is present in atotal amount of up to 10{circumflex over ( )}15 cfu. Further providedherein are kits, wherein the live, purified, and lyophilized populationof bacteria is present in a total amount of 10{circumflex over ( )}3 to10{circumflex over ( )}12 cfu.

In some embodiments, provided herein are kits, wherein the kitcomprises: a first container, wherein the first container compriseslive, purified, and lyophilized population of bacteria that comprises: aplurality of strains of Corynebacterium pseudodiphtheriticum; and aplurality of strains of Dolosigranulum pigrum and; and a secondcontainer, wherein the second container comprises a pharmaceuticallyacceptable excipient. Further provided herein is a kit, wherein thestrain of Corynebacterium pseudodiphtheriticum is selected from a strainlisted in Table 1. Further provided herein is a kit, wherein theDolosigranulum pigrum is selected from a strain listed in Table 2.Further provided herein is a pharmaceutical composition comprising amixture listed in Tables 4-7. Further provided herein are kits, whereinthe live, purified, and lyophilized population of bacteria is present inan amount sufficient for treatment of a respiratory condition. Furtherprovided herein are kits, wherein the live, purified, and lyophilizedpopulation of bacteria is present in a total amount of up to10{circumflex over ( )}15 cfu. Further provided herein are kits, whereinthe live, purified, and lyophilized population of bacteria is present ina total amount of 10{circumflex over ( )}3 to 10{circumflex over ( )}12cfu.

In some embodiments, provided herein are kits, wherein the kitcomprises: a first container, wherein the first container compriseslive, purified, and lyophilized population of bacteria present in atotal amount of at least 10{circumflex over ( )}3 cfu that comprises: astrain of Corynebacterium pseudodiphtheriticum; and a strain ofDolosigranulum pigrum; and a second container, wherein the secondcontainer comprises a pharmaceutically acceptable excipient. Furtherprovided herein is a kit, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a kit, wherein the Dolosigranulum pigrum isselected from a strain listed in Table 2. Further provided herein arekits, wherein the live, purified, and lyophilized population of bacteriais present in an amount sufficient for treatment of a respiratorycondition.

In some embodiments, provided herein are methods for treatment of aneurological condition, comprising: administering to a subject having aneurological condition: a population of purified, live bacteriacomprising at least one strain of bacteria present in an amountsufficient for reduction in incidence of colonization of a pathogenicbacterium in the nasal cavity, wherein the at least one strain ofbacteria is isolated from upper respiratory tract of a donor. Furtherprovided herein is a method, wherein the pathogenic bacterium comprisesStaphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosaor Burkholderia pseudomallei. Further provided herein is a method,wherein the pathogenic bacterium a strain listed Table 3.Corynebacterium pseudodiphtheriticum; and at least one strain ofDolosigranulum pigrum. Further provided herein is a method, wherein theneurological condition is Parkinson's disease (PD), incidental Lewy bodydisorder (iLBD), dementia with Lewy bodies (DLB), Alzheimer's disease(AD), multiple system atrophy (MSA), progressive supranuclear palsy(PSP), frontotemporal dementia (FTD), amyotrophic lateral sclerosis(ALS), pure autonomic failure (PAF), schizophrenia, or Creutzfeldt-Jakobdisease (CJD). Further provided herein are methods wherein, wherein thesubject has a deficit in olfactory perception. Further provided hereinare methods, wherein the live, purified population of bacteria isadministered intranasally. Further provided herein are methods, whereinthe live, purified population of bacteria is administered orally.Further provided herein are methods, wherein the subject is an infant.Further provided herein are methods, wherein the subject is a child.Further provided herein are methods, wherein the subject is an adult.Further provided herein are methods, wherein the adult is 65 years orolder. Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is present in a total amount of up to10{circumflex over ( )}5 cfu. Further provided herein are methods,wherein the live, purified population of bacteria is present in a totalamount of 10{circumflex over ( )}3 to 10{circumflex over ( )}12 cfu.Further provided herein is a method, wherein the species ofCorynebacterium is C. accolens, C. afermentans, C. ammoniagenes, C.amycolatum, C. argentoratense, C. aquaticum, C. auris, C. bovis, C.diphtheria, C. equi (now Rhodococcus equi), C. efficiens, C. flavescens,C. glucuronolyticum, C. glutamicum, C. granulosum, C. haemolyticum, C.halofytica, C. kroppenstedtii, C. jeikeium, C. macginleyi, C.matruchotii, C. minutissimum, C. parvum (Propionibacterium acnes), C.paurometabolum, C. propinquum, C. pseudodiphtheriticum (C. hofmannii),C. pseudotuberculosis, C. ovis, C. pyogenes—Trueperella pyogenes, C.urealyticum, C. renale, C. spec, C. striatum, C. tenuis, C. ulcerans, C.urealyticum, or C. xerosis. Further provided herein is a method, whereinthe strain of Corynebacterium pseudodiphtheriticum is selected from astrain listed in Table 1. Further provided herein is a method, whereinthe Dolosigranulum pigrum is selected from a strain listed in Table 2.Further provided herein is a method, wherein the strain ofCorynebacterium pseudodiphtheriticum is selected from a strain listed inTable 1, and wherein the Dolosigranulum pigrum is selected from a strainlisted in Table 2. Further provided herein is a pharmaceuticalcomposition comprising a mixture listed in Tables 4-7.

In some embodiments, provided herein are methods for microbiomemodification in a subject, comprising: intranasally administering to asubject in need thereof: a population of purified, live bacteriacomprising at least one strain of bacteria present in an amountsufficient for treatment of a neurological condition, wherein the atleast one strain of bacteria is isolated from upper respiratory tract ofa donor. Corynebacterium pseudodiphtheriticum; and at least one strainof Dolosigranulum pigrum. Further provided herein is a method, whereinthe neurological condition is Parkinson's disease (PD), incidental Lewybody disorder (iLBD), dementia with Lewy bodies (DLB), Alzheimer'sdisease (AD), multiple system atrophy (MSA), progressive supranuclearpalsy (PSP), frontotemporal dementia (FTD), amyotrophic lateralsclerosis (ALS), pure autonomic failure (PAF), schizophrenia,Creutzfeldt-Jakob disease (CJD), autism spectrum disorder (ASD),posttraumatic stress disorder (PTSD), anxiety, or depression. In someembodiments, the ASD is autistic disorder, pervasive developmentaldisorder—not otherwise specified (PDD-NOS), Asperger Syndrome, ChildhoodDisintegrative Disorder (CDD), or Rett Syndrome. In some embodiments,the anxiety is generalized anxiety disorder, obsessive-compulsivedisorder, panic disorder, post-traumatic stress disorder, or socialphobia. Further provided herein are methods wherein, wherein the subjecthas a deficit in olfactory perception. Further provided herein aremethods, wherein the live, purified population of bacteria isadministered intranasally. Further provided herein are methods, whereinthe live, purified population of bacteria is administered orally.Further provided herein are methods, wherein the subject is an infant.Further provided herein are methods, wherein the subject is a child.Further provided herein are methods, wherein the subject is an adult.Further provided herein are methods, wherein the adult is 65 years orolder. Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is present in a total amount of up to10{circumflex over ( )}15 cfu. Further provided herein are methods,wherein the live, purified population of bacteria is present in a totalamount of 10{circumflex over ( )}3 to 10{circumflex over ( )}12 cfu.Further provided herein is a method, wherein the species ofCorynebacterium is C. accolens, C. afermentans, C. ammoniagenes, C.amycolatum, C. argentoratense, C. aquaticum, C. auris, C. bovis, C.diphtheria, C. equi (now Rhodococcus equi), C. efficiens, C. flavescens,C. glucuronolyticum, C. glutamicum, C. granulosum, C. haemolyticum, C.halofytica, C. kroppenstedtii, C. jeikeium, C. macginleyi, C.matruchotii, C. minutissimum, C. parvum (Propionibacterium acnes), C.paurometabolum, C. propinquum, C. pseudodiphtheriticum (C. hofmannii),C. pseudotuberculosis, C. ovis, C. pyogenes—Trueperella pyogenes, C.urealyticum, C. renale, C. spec, C. striatum, C. tenuis, C. ulcerans, C.urealyticum, or C. xerosis. Further provided herein is a method, whereinthe strain of Corynebacterium pseudodiphtheriticum is selected from astrain listed in Table 1. Further provided herein is a method, whereinthe Dolosigranulum pigrum is selected from a strain listed in Table 2.Further provided herein is a method, wherein the strain ofCorynebacterium pseudodiphtheriticum is selected from a strain listed inTable 1, and wherein the Dolosigranulum pigrum is selected from a strainlisted in Table 2. Further provided herein is a pharmaceuticalcomposition comprising a mixture listed in Tables 4-7.

In some embodiments, provided herein are methods for treatment of aneurological condition, comprising: administering to a subject having aneurological infection, a live, purified population of bacteria, whereinthe live, purified population of bacteria comprises: a strain ofCorynebacterium pseudodiphtheriticum; and a strain of Dolosigranulumpigrum. Corynebacterium pseudodiphtheriticum; and at least one strain ofDolosigranulum pigrum. Further provided herein is a method, wherein theneurological condition is Parkinson's disease (PD), incidental Lewy bodydisorder (iLBD), dementia with Lewy bodies (DLB), Alzheimer's disease(AD), multiple system atrophy (MSA), progressive supranuclear palsy(PSP), frontotemporal dementia (FTD), amyotrophic lateral sclerosis(ALS), pure autonomic failure (PAF), schizophrenia, or Creutzfeldt-Jakobdisease (CJD). Further provided herein are methods wherein, wherein thesubject has a deficit in olfactory perception. Further provided hereinare methods, wherein the live, purified population of bacteria isadministered intranasally. Further provided herein are methods, whereinthe live, purified population of bacteria is administered orally.Further provided herein are methods, wherein the subject is an infant.Further provided herein are methods, wherein the subject is a child.Further provided herein are methods, wherein the subject is an adult.Further provided herein are methods, wherein the adult is 65 years orolder. Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is present in a total amount of up to10{circumflex over ( )}5 cfu. Further provided herein are methods,wherein the live, purified population of bacteria is present in a totalamount of 10{circumflex over ( )}3 to 10{circumflex over ( )}12 cfu.Further provided herein is a method, wherein the species ofCorynebacterium is C. accolens, C. afermentans, C. ammoniagenes, C.amycolatum, C. argentoratense, C. aquaticum, C. auris, C. bovis, C.diphtheria, C. equi (now Rhodococcus equi), C. efficiens, C. flavescens,C. glucuronolyticum, C. glutamicum, C. granulosum, C. haemolyticum, C.halofytica, C. kroppenstedtii, C. jeikeium, C. macginleyi, C.matruchotii, C. minutissimum, C. parvum (Propionibacterium acnes), C.paurometabolum, C. propinquum, C. pseudodiphtheriticum (C. hofmannii),C. pseudotuberculosis, C. ovis, C. pyogenes—Trueperella pyogenes, C.urealyticum, C. renale, C. spec, C. striatum, C. tenuis, C. ulcerans, C.urealyticum, or C. xerosis. Further provided herein is a method, whereinthe strain of Corynebacterium pseudodiphtheriticum is selected from astrain listed in Table 1. Further provided herein is a method, whereinthe Dolosigranulum pigrum is selected from a strain listed in Table 2.Further provided herein is a method, wherein the strain ofCorynebacterium pseudodiphtheriticum is selected from a strain listed inTable 1, and wherein the Dolosigranulum pigrum is selected from a strainlisted in Table 2. Further provided herein is a pharmaceuticalcomposition comprising a mixture listed in Tables 4-7.

In some embodiments, provided herein are methods for treatment of aneurological condition, comprising: administering to a subject having aneurological condition, a live, purified population of bacteria, whereinthe live, purified population of bacteria comprises a plurality ofspecies of Corynebacterium. Corynebacterium pseudodiphtheriticum; and atleast one strain of Dolosigranulum pigrum. Further provided herein is amethod, wherein the neurological condition is Parkinson's disease (PD),incidental Lewy body disorder (iLBD), dementia with Lewy bodies (DLB),Alzheimer's disease (AD), multiple system atrophy (MSA), progressivesupranuclear palsy (PSP), frontotemporal dementia (FTD), amyotrophiclateral sclerosis (ALS), pure autonomic failure (PAF), schizophrenia,Creutzfeldt-Jakob disease (CJD), or autism spectrum disorder (ASD).Further provided herein are methods, wherein the ASD is autisticdisorder, pervasive developmental disorder—not otherwise specified(PDD-NOS), Asperger Syndrome, Childhood Disintegrative Disorder (CDD),or Rett Syndrome. Further provided herein are methods wherein, whereinthe subject has a deficit in olfactory perception. Further providedherein are methods, wherein the live, purified population of bacteria isadministered intranasally. Further provided herein are methods, whereinthe live, purified population of bacteria is administered orally.Further provided herein are methods, wherein the subject is an infant.Further provided herein are methods, wherein the subject is a child.Further provided herein are methods, wherein the subject is an adult.Further provided herein are methods, wherein the adult is 65 years orolder. Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is present in a total amount of up to10{circumflex over ( )}5 cfu. Further provided herein are methods,wherein the live, purified population of bacteria is present in a totalamount of 10{circumflex over ( )}3 to 10{circumflex over ( )}12 cfu.Further provided herein is a method, wherein the species ofCorynebacterium is C. accolens, C. afermentans, C. ammoniagenes, C.amycolatum, C. argentoratense, C. aquaticum, C. auris, C. bovis, C.diphtheria, C. equi (now Rhodococcus equi), C. efficiens, C. flavescens,C. glucuronolyticum, C. glutamicum, C. granulosum, C. haemolyticum, C.halofytica, C. kroppenstedtii, C. jeikeium, C. macginleyi, C.matruchotii, C. minutissimum, C. parvum (Propionibacterium acnes), C.paurometabolum, C. propinquum, C. pseudodiphtheriticum (C. hofmannii),C. pseudotuberculosis, C. ovis, C. pyogenes—Trueperella pyogenes, C.urealyticum, C. renale, C. spec, C. striatum, C. tenuis, C. ulcerans, C.urealyticum, or C. xerosis. Further provided herein is a method, whereinthe strain of Corynebacterium pseudodiphtheriticum is selected from astrain listed in Table 1. Further provided herein is a method, whereinthe Dolosigranulum pigrum is selected from a strain listed in Table 2.Further provided herein is a method, wherein the strain ofCorynebacterium pseudodiphtheriticum is selected from a strain listed inTable 1, and wherein the Dolosigranulum pigrum is selected from a strainlisted in Table 2. Further provided herein is a pharmaceuticalcomposition comprising a mixture listed in Tables 4-7.

In some embodiments, provided herein are methods for treatment of aneurological condition, comprising: administering to a subject having aneurological condition, a live, purified population of bacteria, whereinthe live, purified population of bacteria comprises: a plurality ofstrains of Dolosigranulum pigrum. Corynebacterium pseudodiphtheriticum;and at least one strain of Dolosigranulum pigrum. Further providedherein is a method, wherein the neurological condition is Parkinson'sdisease (PD), incidental Lewy body disorder (iLBD), dementia with Lewybodies (DLB), Alzheimer's disease (AD), multiple system atrophy (MSA),progressive supranuclear palsy (PSP), frontotemporal dementia (FTD),amyotrophic lateral sclerosis (ALS), pure autonomic failure (PAF),schizophrenia, or Creutzfeldt-Jakob disease (CJD). Further providedherein are methods wherein, wherein the subject has a deficit inolfactory perception. Further provided herein are methods, wherein thelive, purified population of bacteria is administered intranasally.Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is administered orally. Further provided hereinare methods, wherein the subject is an infant. Further provided hereinare methods, wherein the subject is a child. Further provided herein aremethods, wherein the subject is an adult. Further provided herein aremethods, wherein the adult is 65 years or older. Further provided hereinare methods, wherein the live, purified population of bacteria ispresent in a total amount of up to 10{circumflex over ( )}15 cfu.Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is present in a total amount of 10{circumflexover ( )}3 to 10{circumflex over ( )}12 cfu. Further provided herein isa method, wherein the species of Corynebacterium is C. accolens, C.afermentans, C. ammoniagenes, C. amycolatum, C. argentoratense, C.aquaticum, C. auris, C. bovis, C. diphtheria, C. equi (now Rhodococcusequi), C. efficiens, C. flavescens, C. glucuronolyticum, C. glutamicum,C. granulosum, C. haemolyticum, C. halofytica, C. kroppenstedtii, C.jeikeium, C. macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. Furtherprovided herein is a method, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a method, wherein the Dolosigranulum pigrumis selected from a strain listed in Table 2. Further provided herein isa method, wherein the strain of Corynebacterium pseudodiphtheriticum isselected from a strain listed in Table 1, and wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a pharmaceutical composition comprising a mixture listed inTables 4-7.

In some embodiments, provided herein are methods for treatment of aneurological condition, comprising: administering to a subject having aneurological condition, a live, purified population of bacteria, whereinthe live, purified population of bacteria comprises: a plurality ofstrains of Corynebacterium pseudodiphtheriticum; and at least one strainof Dolosigranulum pigrum. Further provided herein is a method, whereinthe neurological condition is Parkinson's disease (PD), incidental Lewybody disorder (iLBD), dementia with Lewy bodies (DLB), Alzheimer'sdisease (AD), multiple system atrophy (MSA), progressive supranuclearpalsy (PSP), frontotemporal dementia (FTD), amyotrophic lateralsclerosis (ALS), pure autonomic failure (PAF), schizophrenia,Creutzfeldt-Jakob disease (CJD), autism spectrum disorder (ASD), orposttraumatic stress disorder (PTSD), anxiety, or depression. In someembodiments, the ASD is autistic disorder, pervasive developmentaldisorder—not otherwise specified (PDD-NOS), Asperger Syndrome, ChildhoodDisintegrative Disorder (CDD), or Rett Syndrome. In some embodiments,the anxiety is generalized anxiety disorder, obsessive-compulsivedisorder, panic disorder, post-traumatic stress disorder, or socialphobia. Further provided herein are methods wherein, wherein the subjecthas a deficit in olfactory perception. Further provided herein aremethods, wherein the live, purified population of bacteria isadministered intranasally. Further provided herein are methods, whereinthe live, purified population of bacteria is administered orally.Further provided herein are methods, wherein the subject is an infant.Further provided herein are methods, wherein the subject is a child.Further provided herein are methods, wherein the subject is an adult.Further provided herein are methods, wherein the adult is 65 years orolder. Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is present in a total amount of up to10{circumflex over ( )}15 cfu. Further provided herein are methods,wherein the live, purified population of bacteria is present in a totalamount of 10{circumflex over ( )}3 to 10{circumflex over ( )}12 cfu.Further provided herein is a method, wherein the species ofCorynebacterium is C. accolens, C. afermentans, C. ammoniagenes, C.amycolatum, C. argentoratense, C. aquaticum, C. auris, C. bovis, C.diphtheria, C. equi (now Rhodococcus equi), C. efficiens, C. flavescens,C. glucuronolyticum, C. glutamicum, C. granulosum, C. haemolyticum, C.halofytica, C. kroppenstedtii, C. jeikeium, C. macginleyi, C.matruchotii, C. minutissimum, C. parvum (Propionibacterium acnes), C.paurometabolum, C. propinquum, C. pseudodiphtheriticum (C. hofmannii),C. pseudotuberculosis, C. ovis, C. pyogenes—Trueperella pyogenes, C.urealyticum, C. renale, C. spec, C. striatum, C. tenuis, C. ulcerans, C.urealyticum, or C. xerosis. Further provided herein is a method, whereinthe strain of Corynebacterium pseudodiphtheriticum is selected from astrain listed in Table 1. Further provided herein is a method, whereinthe Dolosigranulum pigrum is selected from a strain listed in Table 2.Further provided herein is a method, wherein the strain ofCorynebacterium pseudodiphtheriticum is selected from a strain listed inTable 1, and wherein the Dolosigranulum pigrum is selected from a strainlisted in Table 2. Further provided herein is a pharmaceuticalcomposition comprising a mixture listed in Tables 4-7.

In some embodiments, provided herein are methods for treatment ofParkinson's disease, comprising: administering to a subject havingParkinson's disease a live, purified population of bacteria, wherein thelive, purified population of bacteria comprises: at least one species ofCorynebacterium, optionally at least one strain of Corynebacteriumpseudodiphtheriticum; and optionally, at least one strain ofDolosigranulum pigrum. Further provided herein are methods, wherein thelive, purified population of bacteria is administered intranasally.Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is administered orally. Further provided hereinare methods, wherein the subject is an infant. Further provided hereinare methods, wherein the subject is a child. Further provided herein aremethods, wherein the subject is an adult. Further provided herein aremethods, wherein the adult is 65 years or older. Further provided hereinare methods, wherein the live, purified population of bacteria ispresent in a total amount of up to 10{circumflex over ( )}5 cfu. Furtherprovided herein are methods, wherein the live, purified population ofbacteria is present in a total amount of 10{circumflex over ( )}3 to10{circumflex over ( )}12 cfu. Further provided herein is a method,wherein the species of Corynebacterium is C. accolens, C. afermentans,C. ammoniagenes, C. amycolatum, C. argentoratense, C. aquaticum, C.auris, C. bovis, C. diphtheria, C. equi (now Rhodococcus equi), C.efficiens, C. flavescens, C. glucuronolyticum, C. glutamicum, C.granulosum, C. haemolyticum, C. halofytica, C. kroppenstedtii, C.jeikeium, C. macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. Furtherprovided herein is a method, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a method, wherein the Dolosigranulum pigrumis selected from a strain listed in Table 2. Further provided herein isa method, wherein the strain of Corynebacterium pseudodiphtheriticum isselected from a strain listed in Table 1, and wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a pharmaceutical composition comprising a mixture listed inTables 4-7.

In some embodiments, provided herein are methods for treatment ofincidental Lewy body disorder, comprising: administering to a subjecthaving a incidental Lewy body disorder a live, purified population ofbacteria, wherein the live, purified population of bacteria comprises:at least one species of Corynebacterium, optionally at least one strainof Corynebacterium pseudodiphtheriticum; and optionally, at least onestrain of Dolosigranulum pigrum. Further provided herein are methods,wherein the live, purified population of bacteria is administeredintranasally. Further provided herein are methods, wherein the live,purified population of bacteria is administered orally. Further providedherein are methods, wherein the subject is an infant. Further providedherein are methods, wherein the subject is a child. Further providedherein are methods, wherein the subject is an adult. Further providedherein are methods, wherein the adult is 65 years or older. Furtherprovided herein are methods, wherein the live, purified population ofbacteria is present in a total amount of up to 10{circumflex over ( )}15cfu. Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is present in a total amount of 10{circumflexover ( )}3 to 10{circumflex over ( )}12 cfu. Further provided herein isa method, wherein the species of Corynebacterium is C. accolens, C.afermentans, C. ammoniagenes, C. amycolatum, C. argentoratense, C.aquaticum, C. auris, C. bovis, C. diphtheria, C. equi (now Rhodococcusequi), C. efficiens, C. flavescens, C. glucuronolyticum, C. glutamicum,C. granulosum, C. haemolyticum, C. halofytica, C. kroppenstedtii, C.jeikeium, C. macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. Furtherprovided herein is a method, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a method, wherein the Dolosigranulum pigrumis selected from a strain listed in Table 2. Further provided herein isa method, wherein the strain of Corynebacterium pseudodiphtheriticum isselected from a strain listed in Table 1, and wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a pharmaceutical composition comprising a mixture listed inTables 4-7.

In some embodiments, provided herein are methods for treatment ofdementia with Lewy bodies, comprising: administering to a subject havingdementia with Lewy bodies a live, purified population of bacteria,wherein the live, purified population of bacteria comprises: at leastone species of Corynebacterium, optionally at least one strain ofCorynebacterium pseudodiphtheriticum; and optionally, at least onestrain of Dolosigranulum pigrum. Further provided herein are methods,wherein the live, purified population of bacteria is administeredintranasally. Further provided herein are methods, wherein the live,purified population of bacteria is administered orally. Further providedherein are methods, wherein the subject is an infant. Further providedherein are methods, wherein the subject is a child. Further providedherein are methods, wherein the subject is an adult. Further providedherein are methods, wherein the adult is 65 years or older. Furtherprovided herein are methods, wherein the live, purified population ofbacteria is present in a total amount of up to 10{circumflex over ( )}5cfu. Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is present in a total amount of 10{circumflexover ( )}3 to 10{circumflex over ( )}12 cfu. Further provided herein isa method, wherein the species of Corynebacterium is C. accolens, C.afermentans, C. ammoniagenes, C. amycolatum, C. argentoratense, C.aquaticum, C. auris, C. bovis, C. diphtheria, C. equi (now Rhodococcusequi), C. efficiens, C. flavescens, C. glucuronolyticum, C. glutamicum,C. granulosum, C. haemolyticum, C. halofytica, C. kroppenstedtii, C.jeikeium, C. macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. Furtherprovided herein is a method, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a method, wherein the Dolosigranulum pigrumis selected from a strain listed in Table 2. Further provided herein isa method, wherein the strain of Corynebacterium pseudodiphtheriticum isselected from a strain listed in Table 1, and wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a pharmaceutical composition comprising a mixture listed inTables 4-7.

In some embodiments, provided herein are methods for treatment ofAlzheimer's disease, comprising: administering to a subject havingAlzheimer's disease a live, purified population of bacteria, wherein thelive, purified population of bacteria comprises: at least one species ofCorynebacterium, optionally at least one strain of Corynebacteriumpseudodiphtheriticum; and optionally, at least one strain ofDolosigranulum pigrum. Further provided herein are methods, wherein thelive, purified population of bacteria is administered intranasally.Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is administered orally. Further provided hereinare methods, wherein the subject is an infant. Further provided hereinare methods, wherein the subject is a child. Further provided herein aremethods, wherein the subject is an adult. Further provided herein aremethods, wherein the adult is 65 years or older. Further provided hereinare methods, wherein the live, purified population of bacteria ispresent in a total amount of up to 10{circumflex over ( )}5 cfu. Furtherprovided herein are methods, wherein the live, purified population ofbacteria is present in a total amount of 10{circumflex over ( )}3 to10{circumflex over ( )}12 cfu. Further provided herein is a method,wherein the species of Corynebacterium is C. accolens, C. afermentans,C. ammoniagenes, C. amycolatum, C. argentoratense, C. aquaticum, C.auris, C. bovis, C. diphtheria, C. equi (now Rhodococcus equi), C.efficiens, C. flavescens, C. glucuronolyticum, C. glutamicum, C.granulosum, C. haemolyticum, C. halofytica, C. kroppenstedtii, C.jeikeium, C. macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. Furtherprovided herein is a method, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a method, wherein the Dolosigranulum pigrumis selected from a strain listed in Table 2. Further provided herein isa method, wherein the strain of Corynebacterium pseudodiphtheriticum isselected from a strain listed in Table 1, and wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a pharmaceutical composition comprising a mixture listed inTables 4-7.

In some embodiments, provided herein are methods for treatment ofmultiple system atrophy, comprising: administering to a subject havingmultiple system atrophy a live, purified population of bacteria, whereinthe live, purified population of bacteria comprises: at least onespecies of Corynebacterium, optionally at least one strain ofCorynebacterium pseudodiphtheriticum; and optionally, at least onestrain of Dolosigranulum pigrum. Further provided herein are methods,wherein the live, purified population of bacteria is administeredintranasally. Further provided herein are methods, wherein the live,purified population of bacteria is administered orally. Further providedherein are methods, wherein the subject is an infant. Further providedherein are methods, wherein the subject is a child. Further providedherein are methods, wherein the subject is an adult. Further providedherein are methods, wherein the adult is 65 years or older. Furtherprovided herein are methods, wherein the live, purified population ofbacteria is present in a total amount of up to 10{circumflex over ( )}5cfu. Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is present in a total amount of 10{circumflexover ( )}3 to 10{circumflex over ( )}12 cfu. Further provided herein isa method, wherein the species of Corynebacterium is C. accolens, C.afermentans, C. ammoniagenes, C. amycolatum, C. argentoratense, C.aquaticum, C. auris, C. bovis, C. diphtheria, C. equi (now Rhodococcusequi), C. efficiens, C. flavescens, C. glucuronolyticum, C. glutamicum,C. granulosum, C. haemolyticum, C. halofytica, C. kroppenstedtii, C.jeikeium, C. macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. Furtherprovided herein is a method, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a method, wherein the Dolosigranulum pigrumis selected from a strain listed in Table 2. Further provided herein isa method, wherein the strain of Corynebacterium pseudodiphtheriticum isselected from a strain listed in Table 1, and wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a pharmaceutical composition comprising a mixture listed inTables 4-7.

In some embodiments, provided herein are methods for treatment ofprogressive supranuclear palsy, comprising: administering to a subjecthaving progressive supranuclear palsy a live, purified population ofbacteria, wherein the live, purified population of bacteria comprises:at least one species of Corynebacterium, optionally at least one strainof Corynebacterium pseudodiphtheriticum; and optionally, at least onestrain of Dolosigranulum pigrum. Further provided herein are methods,wherein the live, purified population of bacteria is administeredintranasally. Further provided herein are methods, wherein the live,purified population of bacteria is administered orally. Further providedherein are methods, wherein the subject is an infant. Further providedherein are methods, wherein the subject is a child. Further providedherein are methods, wherein the subject is an adult. Further providedherein are methods, wherein the adult is 65 years or older. Furtherprovided herein are methods, wherein the live, purified population ofbacteria is present in a total amount of up to 10{circumflex over ( )}5cfu. Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is present in a total amount of 10{circumflexover ( )}3 to 10{circumflex over ( )}12 cfu. Further provided herein isa method, wherein the species of Corynebacterium is C. accolens, C.afermentans, C. ammoniagenes, C. amycolatum, C. argentoratense, C.aquaticum, C. auris, C. bovis, C. diphtheria, C. equi (now Rhodococcusequi), C. efficiens, C. flavescens, C. glucuronolyticum, C. glutamicum,C. granulosum, C. haemolyticum, C. halofytica, C. kroppenstedtii, C.jeikeium, C. macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. Furtherprovided herein is a method, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a method, wherein the Dolosigranulum pigrumis selected from a strain listed in Table 2. Further provided herein isa method, wherein the strain of Corynebacterium pseudodiphtheriticum isselected from a strain listed in Table 1, and wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a pharmaceutical composition comprising a mixture listed inTables 4-7.

In some embodiments, provided herein are methods for treatment offrontotemporal dementia, comprising: administering to a subject havingfrontotemporal dementia a live, purified population of bacteria, whereinthe live, purified population of bacteria comprises: at least onespecies of Corynebacterium, optionally at least one strain ofCorynebacterium pseudodiphtheriticum; and optionally, at least onestrain of Dolosigranulum pigrum. Further provided herein are methods,wherein the live, purified population of bacteria is administeredintranasally. Further provided herein are methods, wherein the live,purified population of bacteria is administered orally. Further providedherein are methods, wherein the subject is an infant. Further providedherein are methods, wherein the subject is a child. Further providedherein are methods, wherein the subject is an adult. Further providedherein are methods, wherein the adult is 65 years or older. Furtherprovided herein are methods, wherein the live, purified population ofbacteria is present in a total amount of up to 10{circumflex over ( )}5cfu. Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is present in a total amount of 10{circumflexover ( )}3 to 10{circumflex over ( )}12 cfu. Further provided herein isa method, wherein the species of Corynebacterium is C. accolens, C.afermentans, C. ammoniagenes, C. amycolatum, C. argentoratense, C.aquaticum, C. auris, C. bovis, C. diphtheria, C. equi (now Rhodococcusequi), C. efficiens, C. flavescens, C. glucuronolyticum, C. glutamicum,C. granulosum, C. haemolyticum, C. halofytica, C. kroppenstedtii, C.jeikeium, C. macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. Furtherprovided herein is a method, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a method, wherein the Dolosigranulum pigrumis selected from a strain listed in Table 2. Further provided herein isa method, wherein the strain of Corynebacterium pseudodiphtheriticum isselected from a strain listed in Table 1, and wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a pharmaceutical composition comprising a mixture listed inTables 4-7.

In some embodiments, provided herein are methods for treatment ofamyotrophic lateral sclerosis, comprising: administering to a subjecthaving amyotrophic lateral sclerosis a live, purified population ofbacteria, wherein the live, purified population of bacteria comprises:at least one species of Corynebacterium, optionally at least one strainof Corynebacterium pseudodiphtheriticum; and optionally, at least onestrain of Dolosigranulum pigrum. Further provided herein are methods,wherein the live, purified population of bacteria is administeredintranasally. Further provided herein are methods, wherein the live,purified population of bacteria is administered orally. Further providedherein are methods, wherein the subject is an infant. Further providedherein are methods, wherein the subject is a child. Further providedherein are methods, wherein the subject is an adult. Further providedherein are methods, wherein the adult is 65 years or older. Furtherprovided herein are methods, wherein the live, purified population ofbacteria is present in a total amount of up to 10{circumflex over ( )}5cfu. Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is present in a total amount of 10{circumflexover ( )}3 to 10{circumflex over ( )}12 cfu. Further provided herein isa method, wherein the species of Corynebacterium is C. accolens, C.afermentans, C. ammoniagenes, C. amycolatum, C. argentoratense, C.aquaticum, C. auris, C. bovis, C. diphtheria, C. equi (now Rhodococcusequi), C. efficiens, C. flavescens, C. glucuronolyticum, C. glutamicum,C. granulosum, C. haemolyticum, C. halofytica, C. kroppenstedtii, C.jeikeium, C. macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. Furtherprovided herein is a method, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a method, wherein the Dolosigranulum pigrumis selected from a strain listed in Table 2. Further provided herein isa method, wherein the strain of Corynebacterium pseudodiphtheriticum isselected from a strain listed in Table 1, and wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a pharmaceutical composition comprising a mixture listed inTables 4-7.

In some embodiments, provided herein are methods for treatment of pureautonomic failure, comprising: administering to a subject having pureautonomic failure a live, purified population of bacteria, wherein thelive, purified population of bacteria comprises: at least one species ofCorynebacterium, optionally at least one strain of Corynebacteriumpseudodiphtheriticum; and optionally, at least one strain ofDolosigranulum pigrum. Further provided herein are methods, wherein thelive, purified population of bacteria is administered intranasally.Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is administered orally. Further provided hereinare methods, wherein the subject is an infant. Further provided hereinare methods, wherein the subject is a child. Further provided herein aremethods, wherein the subject is an adult. Further provided herein aremethods, wherein the adult is 65 years or older. Further provided hereinare methods, wherein the live, purified population of bacteria ispresent in a total amount of up to 10{circumflex over ( )}5 cfu. Furtherprovided herein are methods, wherein the live, purified population ofbacteria is present in a total amount of 10{circumflex over ( )}3 to10{circumflex over ( )}12 cfu. Further provided herein is a method,wherein the species of Corynebacterium is C. accolens, C. afermentans,C. ammoniagenes, C. amycolatum, C. argentoratense, C. aquaticum, C.auris, C. bovis, C. diphtheria, C. equi (now Rhodococcus equi), C.efficiens, C. flavescens, C. glucuronolyticum, C. glutamicum, C.granulosum, C. haemolyticum, C. halofytica, C. kroppenstedtii, C.jeikeium, C. macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. Furtherprovided herein is a method, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a method, wherein the Dolosigranulum pigrumis selected from a strain listed in Table 2. Further provided herein isa method, wherein the strain of Corynebacterium pseudodiphtheriticum isselected from a strain listed in Table 1, and wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a pharmaceutical composition comprising a mixture listed inTables 4-7.

In some embodiments, provided herein are methods for treatment ofschizophrenia, comprising: administering to a subject havingschizophrenia a live, purified population of bacteria, wherein the live,purified population of bacteria comprises: at least one species ofCorynebacterium, optionally at least one strain of Corynebacteriumpseudodiphtheriticum; and optionally, at least one strain ofDolosigranulum pigrum. Further provided herein are methods, wherein thelive, purified population of bacteria is administered intranasally.Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is administered orally. Further provided hereinare methods, wherein the subject is an infant. Further provided hereinare methods, wherein the subject is a child. Further provided herein aremethods, wherein the subject is an adult. Further provided herein aremethods, wherein the adult is 65 years or older. Further provided hereinare methods, wherein the live, purified population of bacteria ispresent in a total amount of up to 10{circumflex over ( )}5 cfu. Furtherprovided herein are methods, wherein the live, purified population ofbacteria is present in a total amount of 10{circumflex over ( )}3 to10{circumflex over ( )}12 cfu. Further provided herein is a method,wherein the species of Corynebacterium is C. accolens, C. afermentans,C. ammoniagenes, C. amycolatum, C. argentoratense, C. aquaticum, C.auris, C. bovis, C. diphtheria, C. equi (now Rhodococcus equi), C.efficiens, C. flavescens, C. glucuronolyticum, C. glutamicum, C.granulosum, C. haemolyticum, C. halofytica, C. kroppenstedtii, C.jeikeium, C. macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. Furtherprovided herein is a method, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a method, wherein the Dolosigranulum pigrumis selected from a strain listed in Table 2. Further provided herein isa method, wherein the strain of Corynebacterium pseudodiphtheriticum isselected from a strain listed in Table 1, and wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a pharmaceutical composition comprising a mixture listed inTables 4-7.

In some embodiments, provided herein are methods for treatment ofCreutzfeldt-Jakob disease, comprising: administering to a subject havingCreutzfeldt-Jakob disease a live, purified population of bacteria,wherein the live, purified population of bacteria comprises: at leastone species of Corynebacterium, optionally at least one strain ofCorynebacterium pseudodiphtheriticum; and optionally, at least onestrain of Dolosigranulum pigrum. Further provided herein are methods,wherein the live, purified population of bacteria is administeredintranasally. Further provided herein are methods, wherein the live,purified population of bacteria is administered orally. Further providedherein are methods, wherein the subject is an infant. Further providedherein are methods, wherein the subject is a child. Further providedherein are methods, wherein the subject is an adult. Further providedherein are methods, wherein the adult is 65 years or older. Furtherprovided herein are methods, wherein the live, purified population ofbacteria is present in a total amount of up to 10{circumflex over ( )}5cfu. Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is present in a total amount of 10{circumflexover ( )}3 to 10{circumflex over ( )}12 cfu. Further provided herein isa method, wherein the species of Corynebacterium is C. accolens, C.afermentans, C. ammoniagenes, C. amycolatum, C. argentoratense, C.aquaticum, C. auris, C. bovis, C. diphtheria, C. equi (now Rhodococcusequi), C. efficiens, C. flavescens, C. glucuronolyticum, C. glutamicum,C. granulosum, C. haemolyticum, C. halofytica, C. kroppenstedtii, C.jeikeium, C. macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. Furtherprovided herein is a method, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a method, wherein the Dolosigranulum pigrumis selected from a strain listed in Table 2. Further provided herein isa method, wherein the strain of Corynebacterium pseudodiphtheriticum isselected from a strain listed in Table 1, and wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a pharmaceutical composition comprising a mixture listed inTables 4-7.

In some embodiments, provided herein are methods for treatment of autismspectrum disorder (ASD), comprising: administering to a subject havingASD a live, purified population of bacteria, wherein the live, purifiedpopulation of bacteria comprises: at least one species ofCorynebacterium, optionally at least one strain of Corynebacteriumpseudodiphtheriticum; and optionally, at least one strain ofDolosigranulum pigrum. Further provided herein are methods, wherein theASD is autistic disorder, pervasive developmental disorder—not otherwisespecified (PDD-NOS), Asperger Syndrome, Childhood DisintegrativeDisorder (CDD), or Rett Syndrome. Further provided herein are methods,wherein the live, purified population of bacteria is administeredintranasally. Further provided herein are methods, wherein the live,purified population of bacteria is administered orally. Further providedherein are methods, wherein the subject is an infant. Further providedherein are methods, wherein the subject is a child. Further providedherein are methods, wherein the subject is an adult. Further providedherein are methods, wherein the adult is 65 years or older. Furtherprovided herein are methods, wherein the live, purified population ofbacteria is present in a total amount of up to 10{circumflex over ( )}15cfu. Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is present in a total amount of 10{circumflexover ( )}3 to 10{circumflex over ( )}12 cfu. Further provided herein isa method, wherein the species of Corynebacterium is C. accolens, C.afermentans, C. ammoniagenes, C. amycolatum, C. argentoratense, C.aquaticum, C. auris, C. bovis, C. diphtheria, C. equi (now Rhodococcusequi), C. efficiens, C. flavescens, C. glucuronolyticum, C. glutamicum,C. granulosum, C. haemolyticum, C. halofytica, C. kroppenstedtii, C.jeikeium, C. macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. Furtherprovided herein is a method, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a method, wherein the Dolosigranulum pigrumis selected from a strain listed in Table 2. Further provided herein isa method, wherein the strain of Corynebacterium pseudodiphtheriticum isselected from a strain listed in Table 1, and wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a pharmaceutical composition comprising a mixture listed inTables 4-7.

In some embodiments, provided herein are methods for treatment ofposttraumatic stress disorder (PTSD), comprising: administering to asubject having PTSD a live, purified population of bacteria, wherein thelive, purified population of bacteria comprises: at least one species ofCorynebacterium, optionally at least one strain of Corynebacteriumpseudodiphtheriticum; and optionally, at least one strain ofDolosigranulum pigrum. Further provided herein are methods, wherein thelive, purified population of bacteria is administered intranasally.Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is administered orally. Further provided hereinare methods, wherein the subject is an infant. Further provided hereinare methods, wherein the subject is a child. Further provided herein aremethods, wherein the subject is an adult. Further provided herein aremethods, wherein the adult is 65 years or older. Further provided hereinare methods, wherein the live, purified population of bacteria ispresent in a total amount of up to 10{circumflex over ( )}5 cfu. Furtherprovided herein are methods, wherein the live, purified population ofbacteria is present in a total amount of 10{circumflex over ( )}3 to10{circumflex over ( )}12 cfu. Further provided herein is a method,wherein the species of Corynebacterium is C. accolens, C. afermentans,C. ammoniagenes, C. amycolatum, C. argentoratense, C. aquaticum, C.auris, C. bovis, C. diphtheria, C. equi (now Rhodococcus equi), C.efficiens, C. flavescens, C. glucuronolyticum, C. glutamicum, C.granulosum, C. haemolyticum, C. halofytica, C. kroppenstedtii, C.jeikeium, C. macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. Furtherprovided herein is a method, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a method, wherein the Dolosigranulum pigrumis selected from a strain listed in Table 2. Further provided herein isa method, wherein the strain of Corynebacterium pseudodiphtheriticum isselected from a strain listed in Table 1, and wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a pharmaceutical composition comprising a mixture listed inTables 4-7.

In some embodiments, provided herein are methods for treatment ofanxiety, comprising: administering to a subject having anxiety a live,purified population of bacteria, wherein the live, purified populationof bacteria comprises: at least one species of Corynebacterium,optionally at least one strain of Corynebacterium pseudodiphtheriticum;and optionally, at least one strain of Dolosigranulum pigrum. In someembodiments, the anxiety is generalized anxiety disorder,obsessive-compulsive disorder, panic disorder, post-traumatic stressdisorder, or social phobia. Further provided herein are methods, whereinthe live, purified population of bacteria is administered intranasally.Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is administered orally. Further provided hereinare methods, wherein the subject is an infant. Further provided hereinare methods, wherein the subject is a child. Further provided herein aremethods, wherein the subject is an adult. Further provided herein aremethods, wherein the adult is 65 years or older. Further provided hereinare methods, wherein the live, purified population of bacteria ispresent in a total amount of up to 10{circumflex over ( )}15 cfu.Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is present in a total amount of 10{circumflexover ( )}3 to 10{circumflex over ( )}12 cfu. Further provided herein isa method, wherein the species of Corynebacterium is C. accolens, C.afermentans, C. ammoniagenes, C. amycolatum, C. argentoratense, C.aquaticum, C. auris, C. bovis, C. diphtheria, C. equi (now Rhodococcusequi), C. efficiens, C. flavescens, C. glucuronolyticum, C. glutamicum,C. granulosum, C. haemolyticum, C. halofytica, C. kroppenstedtii, C.jeikeium, C. macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. Furtherprovided herein is a method, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a method, wherein the Dolosigranulum pigrumis selected from a strain listed in Table 2. Further provided herein isa method, wherein the strain of Corynebacterium pseudodiphtheriticum isselected from a strain listed in Table 1, and wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a pharmaceutical composition comprising a mixture listed inTables 4-7.

In some embodiments, provided herein are methods for treatment ofdepression, comprising: administering to a subject having depression alive, purified population of bacteria, wherein the live, purifiedpopulation of bacteria comprises: at least one species ofCorynebacterium, optionally at least one strain of Corynebacteriumpseudodiphtheriticum; and optionally, at least one strain ofDolosigranulum pigrum. Further provided herein are methods, wherein thelive, purified population of bacteria is administered intranasally.Further provided herein are methods, wherein the live, purifiedpopulation of bacteria is administered orally. Further provided hereinare methods, wherein the subject is an infant. Further provided hereinare methods, wherein the subject is a child. Further provided herein aremethods, wherein the subject is an adult. Further provided herein aremethods, wherein the adult is 65 years or older. Further provided hereinare methods, wherein the live, purified population of bacteria ispresent in a total amount of up to 10{circumflex over ( )}5 cfu. Furtherprovided herein are methods, wherein the live, purified population ofbacteria is present in a total amount of 10{circumflex over ( )}3 to10{circumflex over ( )}12 cfu. Further provided herein is a method,wherein the species of Corynebacterium is C. accolens, C. afermentans,C. ammoniagenes, C. amycolatum, C. argentoratense, C. aquaticum, C.auris, C. bovis, C. diphtheria, C. equi (now Rhodococcus equi), C.efficiens, C. flavescens, C. glucuronolyticum, C. glutamicum, C.granulosum, C. haemolyticum, C. halofytica, C. kroppenstedtii, C.jeikeium, C. macginleyi, C. matruchotii, C. minutissimum, C. parvum(Propionibacterium acnes), C. paurometabolum, C. propinquum, C.pseudodiphtheriticum (C. hofmannii), C. pseudotuberculosis, C. ovis, C.pyogenes—Trueperella pyogenes, C. urealyticum, C. renale, C. spec, C.striatum, C. tenuis, C. ulcerans, C. urealyticum, or C. xerosis. Furtherprovided herein is a method, wherein the strain of Corynebacteriumpseudodiphtheriticum is selected from a strain listed in Table 1.Further provided herein is a method, wherein the Dolosigranulum pigrumis selected from a strain listed in Table 2. Further provided herein isa method, wherein the strain of Corynebacterium pseudodiphtheriticum isselected from a strain listed in Table 1, and wherein the Dolosigranulumpigrum is selected from a strain listed in Table 2. Further providedherein is a pharmaceutical composition comprising a mixture listed inTables 4-7.

EXAMPLES Example 1: Bacterial Mixtures

i. Isolates and mixtures. Described herein are combinations of bacterialstrains that can be used in generation of compositions, includingpharmaceutical compositions for treatment of respiratory tractconditions. In the mixtures that follow, each of the live, purifiedstrains are present in equal CFU amounts to other live, purified strainsin each mixture.

First, mixtures having combinations of two strains are generated. Eachmixture includes that two strains of Corynebacterium listed in Table 1,where an “X” denotes inclusion, are listed in the 44 mixtures (A1 toA44) in Table 4.

TABLE 4 KPL DSM4 0901 KPL18 DSM44 DSM6 DSM1 DSM44 DSM20 DSM20 Mixture1989 4287 04 18 278 922 567 285 300 668 A1 X X A2 X X A3 X X A4 X X A5 XX A6 X X A7 X X A8 X X A9 X X A10 X X A11 X X A12 X X A13 X X A14 X XA15 X X A16 X X A17 X X A18 X X A19 X X A20 X X A21 X X A22 X X A23 X XA24 X X A25 X X A26 X X A27 X X A28 X X A29 X X A30 X X A31 X X A32 X XA33 X X A34 X X A35 X X A36 X X A37 X X A38 X X A39 X X A40 X A41 X A42X X A43 X X A44 X X

Second, mixtures are made that includes two strains of D. pigrum listedin Table 2, where an “X” denotes inclusion, are listed in the 66mixtures (B1 to B66) in Table 5.

TABLE 5 CDC CDC CDC CDC CDC CDC CDC CDC CDC KLP 39- 2949- 4294- 4420-4545- 4709- 4199- 4791- 4791- AMBR AMBR Mixture 1914 95 98 98 98 98 9899 99 99 11 12 B1 X X B2 X X B3 X X B4 X X B5 X X B6 X X B7 X X B8 X XB9 X X B10 X X B11 X X B12 X X B13 X X B14 X X B15 X X B16 X X B17 X XB18 X X B19 X X B20 X X B21 X X B22 X X B23 X X B24 X X B25 X X B26 X XB27 X X B28 X X B29 X X B30 X X B31 X X B32 X X B33 X X B34 X X B35 X XB36 X X B37 X X B38 X X B39 X X B40 X X B41 X X B42 X X B43 X X B44 X XB45 X X B46 X X B47 X X B48 X X B49 X X B50 X X B51 X X B52 X X B53 X XB54 X X B55 X X B56 X X B57 X X B58 X X B59 X X B60 X X B61 X X B62 X XB63 X X B64 X X B65 X X B66 X X

Third, mixtures of Corynebacterium listed in Table 1 are each combinedwith one of the 12 strains of D. pigrum listed in Table 2, where an “X”denotes inclusion, are listed in the 66 mixtures (C1 to C130) in Table6.

TABLE 6 Corynebacterium CDC CDC CDC CDC CDC CDC CDC CDC CDC strain KLP-39- 2949- 4294- 4420- 4545- 4709- 4199- 4791- 4791- AMB AMB Mixture(below) 1914 95 98 98 98 98 98 99 99 99 R11 R12 C1 KPL1989 X C2 DSM44287X C3 090104 X C4 KPL1818 X C5 DSM44278 X C6 DSM6922 X C7 DSM1567 X C8DSM44285 X C9 DSM20300 X C10 DSM20668 X C11 KPL1989 X C12 DSM44287 X C13090104 X C14 KPL1818 X C15 DSM44278 X C16 DSM6922 X C17 DSM1567 X C18DSM44285 X C19 DSM20300 X C20 DSM20668 X C21 KPL1989 X C22 DSM44287 XC23 090104 X C24 KPL1818 X C25 DSM44278 X C26 DSM6922 X C27 DSM1567 XC28 DSM44285 X C29 DSM20300 X C30 DSM20668 X C41 KPL1989 X C42 DSM44287X C43 090104 X C44 KPL1818 X C45 DSM44278 X C46 DSM6922 X C47 DSM1567 XC48 DSM44285 X C49 DSM20300 X C50 DSM20668 X C51 KPL1989 X C52 DSM44287X C53 090104 X C54 KPL1818 X C55 DSM44278 X C56 DSM6922 X C57 DSM1567 XC58 DSM44285 X C59 DSM20300 X C60 DSM20668 X C61 KPL1989 X C62 DSM44287X C63 090104 X C64 KPL1818 X C65 DSM44278 X C66 DSM6922 X C67 DSM1567 XC68 DSM44285 X C69 DSM20300 X C70 DSM20668 X C71 KPL1989 X C72 DSM44287X C73 090104 X C74 KPL1818 X C75 DSM44278 X C76 DSM6922 X C77 DSM1567 XC78 DSM44285 X C79 DSM20300 X C80 DSM20668 X C81 KPL1989 X C82 DSM44287X C83 090104 X C84 KPL1818 X C85 DSM44278 X C86 DSM6922 X C87 DSM1567 XC88 DSM44285 X C89 DSM20300 X C90 DSM20668 X C91 KPL1989 X C92 DSM44287X C93 090104 X C94 KPL1818 X C95 DSM44278 X C96 DSM6922 X C97 DSM1567 XC98 DSM44285 X C99 DSM20300 X C100 DSM20668 X C101 KPL1989 X C102DSM44287 X C103 090104 X C104 KPL1818 X C105 DSM44278 X C106 DSM6922 XC107 DSM1567 X C108 DSM44285 X C109 DSM20300 X C110 DSM20668 X C111KPL1989 X C112 DSM44287 X C113 090104 X C114 KPL1818 X C115 DSM44278 XC116 DSM6922 X C117 DSM1567 X C118 DSM44285 X C119 DSM20300 X C120DSM20668 X C121 KPL1989 X C122 DSM44287 X C123 090104 X C124 KPL1818 XC125 DSM44278 X C126 DSM6922 X C127 DSM1567 X C128 DSM44285 X C129DSM20300 X C130 DSM20668 X

Fourth, a mixture of multiple Corynebacterium strains from Table 1 ismade. In this example, 2, 3, 4, or 5 strains are from difference speciesof Corynebacterium are in the composition. Strains are selected from: C.pseudodiphtheriticum ATCC 10700 and/or JCM 1320; C. amycolatum ATCC49358; C. glutamicum ATCC 13032; and C. striatum ATCC 6940. Thecompositions may include ATCC 10700 and/or JCM 1320 in addition to thestrains from species other than ATCC 10700 and/or JCM 1320.

Fifth, a mixture of two Corynebacterium pseudodiphtheriticum strainsfrom Table 1 is made: ATCC 10700 and JCM 1320, “mixture D1.”

Sixth, mixture D1 is combined with one of the 12 strains of D. pigrumlisted in Table 2, where an “X” denotes inclusion, are listed in the 66mixtures (E1 to E12) in Table 7.

TABLE 7 Mixture D1 (ATCC 10700 CDC CDC CDC CDC CDC CDC CDC CDC CDC andJCM KLP- 39- 2949- 4294- 4420- 4545- 4709- 4199- 4791- 4791- AMB AMBMixture 1320) 1914 95 98 98 98 98 98 99 99 99 R11 R12 E1 X X E2 X X E3 XX E4 X X E5 X X E6 X X E7 X X E8 X X E9 X X E10 X X E11 X X E12 X X

Seventh mixtures of Corynebacterium listed in Table 1 are combined toinclude at least one strain of each of C. pseudodiphtheriticum, C.accolens, and C. amycolatum. For example: ATCC 10700 and/or JCM 1320plus ATCC 49725 and ATCC 49368.

iii. Cultivation from frozen stocks. Bacterial strains are grown at 37°C. with 5% CO2. D. pigrum strains are cultivated from frozen stocks onBBL Columbia Colistin-Nalidixic Acid (CNA) agar with 5% sheep blood (BDDiagnostics) for 2 days. Corynebacterium species are cultivated fromfrozen stocks on BHI agar (e.g., for C. pseudodiphtheriticum and C.propinquum) or BHI agar supplemented with 1% Tween 80 (e.g., for C.accolens) for 1 day. Resuspensions described below are made byharvesting colonies from agar medium and resuspending in 1× phosphatebuffered saline (PBS).

Example 2: MRSA Model Systems

i. Contact-Dependent Assays. Clinical isolates of C.pseudodiphtheriticum and D. pigrum taken from subjects (e.g., fromstrains listed in Table 1 and Table 2, and mixtures from Example 1) areassayed to determine if anti-S. aureus activity is dependent on directphysical contact between the bacteria. Briefly, a sterile 0.2 μm filterdisk is placed on top of the BHIT agar (Brain Heart Infusion (BHI) agar(Becton Dickinson)) seeded with one of the S. aureus strains provided inTable 3 (JE2, LAC, Mu50, or USA 900). Each clinical isolate in asuspension is individually spotted on top of the filter disk so thatnone of the cell suspension physically touched the S. aureus seeded agarplate. Plates are incubated at 28° C. and visually assessed at 24, 72,and 120 hours for the absence or presence of a zone of clearance (ZOC).The absence of a ZOC in the presence of a filter disk indicates thatphysical contact is necessary for anti-S. aureus activity against thecorresponding most sensitive S. aureus strain.

ii. Conditioned Cell Free Medium (CCFM) Preparation and Disk DiffusionAssays. Clinical isolates that produce contact-independent bactericidalanti-S. aureus activity (e.g., from strains listed in Table 1, Table 2,and mixtures from Example 1) are independently cultured in 10 mL BHITbroth overnight at 37° C. with shaking at 190 rpm. Cultures are pelletedby centrifugation, and the supernatant is filter-sterilized with a 2 μmfilter (Corning). One-milliliter of sterile supernatant is retained, andthe remaining supernatant is concentrated (50×) with ammonium sulfateprecipitation. For heat-treatments, 50 μL aliquots of unconcentrated or50× CCFM are incubated at 90° C. for 10 minutes, then allowed to cool.For the disk diffusion assays, the S. aureus strain that is mostsensitive to the corresponding inhibitory activity is cultured on BHIagar overnight at 37° C. The following day, the plate-grown cells arerecovered and diluted to 1×10{circumflex over ( )}8 cells/ml (OD600 of0.1) in BHI broth. A sterile swab is then used to spread the S. aureuscell suspension on BHIT agar as a lawn. The plate is allowed to dry in alaminar flow hood for 30 minutes. Next, a sterile 5 mm diffusion disk isplaced on top of the S. aureus lawn, and 50 μL of unconcentrated CCFM or50× CCFM is inoculated onto the disk. Plates are incubated at 28° C.,and images are taken after 72 hours of incubation.

iii. S. aureus Infection and CCFM Treatment of Galleria mellonellaCaterpillars. Staphylococcus aureus strains JE2, LAC, Mu50, or USA 900are cultured overnight on BHI agar at 37° C. The following day, S.aureus cells are recovered and diluted to 1×10{circumflex over ( )}8cells/ml (OD600=0.1) in PBS. Total CFU are then further adjusted toobtain the required doses; i.e., 10{circumflex over ( )}7 CFU or10{circumflex over ( )}6 CFU in 5 μL of PBS+0.01% bromophenol dye. Forinfections, Galleria mellonella caterpillars (Vanderhorst Wholesale Inc)are utilized within 1 day of receipt. Caterpillars between 200 and 300mg are chosen for infection. Briefly, 5 μL of inoculum that contained10{circumflex over ( )}7 or 10{circumflex over ( )}6 total CFU of S.aureus are injected into the last left proleg using a 10 μL glasssyringe (Hamilton) fitted with a 31G needle. For caterpillars that aretreated with CCFM obtains from strains in Table 1, Table 2, and mixturesfrom Example 1, the caterpillars are maintained at room temperature for1 hour following the S. aureus injection, then refrigerated at 4° C. for12 minutes and then injected with 5 μL of freshly prepared 50× CCFM fromthe clinical isolate (treated) or 50× concentrated BHIT (sham treated).These injections are into the last right proleg. All caterpillars areincubated at 37° C., and survival was monitored over 120 hours.Untouched, and PBS injected caterpillars are included as controls.

iv. Intranasal colonization assay for Methicillin-ResistantStaphylococcus aureus in Mice. Staphylococcus aureus strains JE2, LAC,Mu50, or USA 900 are cultured at 37° C. in either Todd-Hewitt broth(THB) or on Todd-Hewitt agar (THA) (Difco). Brain Heart Infusion (BHI)(Difco) broth and agar are used to grow C. pseudodiphtheriticum and D.pigrum strains (e.g., from strains listed in Table 1, Table 2, andExample 1). CD1 mice (Charles River Laboratories, Wilmington, Mass.) areobtained. Mice are inoculated intranasally with 10 μl droplet of theinocula at the indicated concentrations. Mice are administered1×10{circumflex over ( )}9 CFU total of the bacteria. CD1 mice areinoculated intranasally with: (i) C. pseudodiphtheriticum, (ii) D.pigrum, (iii) C. pseudodiphtheriticum and D. pigrum, or (iv) PBS. Aftertwo days, the mice are administered streptomycin-resistant MRSA (JE2,LAC, Mu50, or USA 900) by the intranasal route, and sacrificed afteranother 2 days. For bacterial enumeration, the mice are euthanized usingisoflurane followed by cervical dislocation, and the nasal tissue ishomogenized and vortexed for 5 min in PBS, and the homogenate is platedon THA with or without streptomycin after appropriate serial dilutions.Bacterial identification is based on antibiotic resistance patterns,colony morphology, and color.

Example 3: Pneumonia Model Systems

i. Growth assay of S. pneumoniae in cell-free conditioned liquid medium.After growth in BHI, D. pigrum or C. pseudodiphtheriticum cells (e.g.,from strains listed in Table 1, Table 2, and mixtures from Example 1)are removed with a 0.22-μM sterile filter yielding cell-free conditionedmedium (CFCM). The pH of the CFCM is adjusted using 2N H2SO4 and 10M KOHto match that of BHI broth alone within 0.02 pH units. S. pneumoniaestrains TIGR4, DBL5, and M270-8 (see Table 3) are each grown on BBLColumbia CNA agar with 5% sheep blood for 1 day, harvested with asterile cotton swab, resuspended to an OD600 of 0.30 in 1× PBS,inoculated at 1:100 into both of D. pigrum or C. pseudodiphtheriticumCFCM and BHI broth and grown for 19-20 hour at 37° C. in static (S.pneumoniae) culture under atmospheric conditions. Growth yield isquantified as OD600 absorbance.

ii. Growth assay for S. pneumoniae in conditioned by mono- vs.co-culture medium. D. pigrum and C. pseudodiphtheriticum strains (e.g.,from strains listed in Table 1, Table 2, and mixtures from Example 1)are grown from freezer stocks. Cells are harvested with sterile cottonswabs and resuspended in sterile PBS to an OD600 nm of 0.5. Cells arethen spotted in 100 μl of 1:1 mixed resuspension on a polycarbonatemembrane on BHI agar medium containing 400 U/mL bovine liver catalase.After 2 days of growth, the polycarbonate membrane with D. pigrum and/orC. pseudodiphtheriticum is removed from each plate leaving cell-freeconditioned agar medium. S. pneumoniae is grown overnight on BBLColumbia CNA agar with 5% sheep blood using a sterile cotton swab, alawn is streaked onto the cell-free conditioned agar medium and allowedto grow for 24 hours. Growth/inhibition is assessed daily andphotographically recorded.

iii. Mouse model. 6- to 8-week-old FVB/N mice are orally gavaged with200 μL of either (i) C. pseudodiphtheriticum, (ii) D. pigrum, (iii) C.pseudodiphtheriticum and D. pigrum (e.g., from strains listed in Table1, Table 2, and mixtures from Example 1), or (iv) sterile water(vehicle) (for the bacteria: 1×10{circumflex over ( )}9 colony-formingunits (CFUs)/mL) immediately before procedure. Pneumonia is induced viadirect intratracheal instillation of Pseudomonas aeruginosa (ATCC 27853)or S. pneumoniae (TIGR4, M270-8, or DBL5). Under isoflurane anesthesia,mice receive a midline cervical incision, and P. aeruginosa or S.pneumoniae is introduced into the trachea via a 29-gauge syringe. Fortymicroliters of 4×10{circumflex over ( )}8 CFUs of bacteria diluted insterile saline is used. Mice are then held vertically for 5 seconds toenhance the delivery into the lungs. Sham mice are treated identicallyexcept that they receive an intratracheal injection of saline. All micereceive antibiotic therapy (gentamicin 0.2 mg/mL, subcutaneously) afterthe surgery to mimic clinical setting. Animals are killed at either 12or 24 hours (for acute studies) or followed 7 days for survival. Foracute studies, mice receive a single dose of (i) C.pseudodiphtheriticum, (ii) D. pigrum, or (iii) C. pseudodiphtheriticumand D. pigrum. For survival studies, mice are treated with (i) C.pseudodiphtheriticum, (ii) D. pigrum, or (iii) C. pseudodiphtheriticumand D. pigrum daily for 7 days and receive antibiotic treatment at 0,12, and 24 hours. Lungs are tested for the presence of P. aeruginosa orS. pneumoniae.

Example 4: Rhinitis Model System

Female BALB/cA mice 2 months old are used. Animals are fed a standardrodent chow diet in a temperature-controlled room (23 degrees C.) on a12 hour light/dark cycle. The immune response of the mice is suppressedby subcutaneous injections of hydrocortisone (Hydrocortisonehemisuccinate 100, Polfa, PL, 100 mg/kg/day) at day 0 and day 4. S.aureus (JE2, LAC, Mu50, or USA 900) is applied intranasally on day 5.Bacterial treatment is performed on day 10. Forty microliters of4×10{circumflex over ( )}8 CFUs of bacteria diluted in sterile saline isused. Mice receive a single dose of (i) C. pseudodiphtheriticum, (ii) D.pigrum, or (iii) C. pseudodiphtheriticum and D. pigrum (e.g., fromstrains listed in Table 1, Table 2, and mixtures from Example 1); or(iv) saline (vehicle). Animals are killed at either 12 or 24 hours orfollowed 7 days for survival, and tissue samples are taken. Blood andinternal organ (e.g., lungs, kidney, liver and spleen) samples aretested for the presence of S. aureus; nasal epithelium is tested forcarriage of S. aureus in control and experimental animals.

Example 5: Allergic Asthma Model System

i. Allergic asthma mouse model. Female C57BL/6 mice, aged 6-8 weeks(Charles River), are maintained in laminar flow rooms at constanttemperature and humidity, with food and water given ad libitum. Mice aretreated with vancomycin and/or neomycin (5 days/week at 12-hr intervals)or with bacteria ((i) C. pseudodiphtheriticum, (ii) D. pigrum, or (iii)C. pseudodiphtheriticum and D. pigrum (e.g., from strains listed inTable 1, Table 2, and mixtures from Example 1)) (3 times/week), starting2 weeks before they are i.v. injected with 5×10{circumflex over ( )}5B16 melanoma cells and continuing throughout the experiment.

For depletion of effector cells, mice are i.v. injected with CD3 F(ab′)2fragments (145-2C11 f(ab′)2) (BioXcell) at a dose of 50 μg/day for 5days/week starting 1 day before tumor injection to deplete T cells orare intraperitoneally (i.p.) injected with 500 μg of α-NK1.1 antibody(PK136) (BioXcell) 1 day before tumor injection, followed by injectionof 200 μg every 5 days throughout the experiment, to deplete NK cells.The efficacy of cell depletion is verified by staining peripheral bloodleukocytes for specific subsets after depletion. In therapeuticexperiments, mice are i.v. injected with 5×10{circumflex over ( )}5 B16melanoma cells and treated starting 7 days after tumor cell injectionwith antibiotics (vancomycin and neomycin) or probiotics ((i) C.pseudodiphtheriticum, (ii) D. pigrum, or (iii) C. pseudodiphtheriticumand D. pigrum) alone or in combination with DTIC, administered i.p. at70 mg/kg (5 days/week). Mice are weighed twice weekly and euthanized atday 21 after tumor injection to count macroscopic lung metastases.

Example 6: Asthma Model Systems

i. Acute asthma model system. Six-week-old female BALB/c mice aresensitized by intraperitoneal (i.p.) administration of an ovalbumin(OVA; 10 μg, grade V; Sigma Chemical Co., St. Louis, Mo., USA) and alum(2.25 mg; Imject, Pierce, Rockford, Ill., USA) mixture. One week afterthe first sensitization, the mixture is administered a second time.Seven days later, the mice inhale 1% OVA via an ultrasonic sprayer(Nescosonic UN-511; Alfresa, Osaka, Japan) for 30 minutes daily forthree successive days (OVA challenge). The mice receive bacteria (i) C.pseudodiphtheriticum, (ii) D. pigrum, or (iii) C. pseudodiphtheriticumand D. pigrum (e.g., strains in listed Table 1, Table 2, and mixturesfrom Example 1); or (iv) PBS (vehicle) in an amount of 1×10{circumflexover ( )}9 colony-forming units/mouse/day, intranasally from one weekbefore primary sensitization to the endpoint of the study. Negativecontrols received only saline instead of OVA at both sensitizations andairway challenge. Positive controls received nothing more after OVAsensitization.

Clinical evaluations in vivo. Airway hyperresponsiveness (AHR) inresponse to inhaled methacholine (MeCh; Sigma Chemical Co.),administered 24 hours after OVA challenge, is measured in conscious,unrestrained mice using a barometric whole-body plethysmograph (Buxco;EMKA Technologies, Paris, France). Briefly, mice are placed in awhole-body chamber, and basal readings is obtained for 3 minutes andaveraged. Aerosolized saline followed by 5-50 mg/mL MeCh are inhaled for3 minutes after each MeCh inhalation. Treg cells are depleted usinganti-CD25 monoclonal antibody (mAb). Briefly, mice received 250 μg ofrat anti-mouse CD25 mAb (clone PC61; eBioscience, San Diego, Calif.,USA) i.p. in 400 μL of normal saline one day before 1% OVA challenge.Control mice are injected with 250 μg of rat IgG1 (Sigma Chemical Co.).

Bronchoalveolar lavage (BAL) fluid analysis. After measurement of AHR,the mice are anesthetized by i.p. administration of ketamine-xylazine,and the trachea is immediately exposed. The airways are lavaged througha tracheal cannula, two times with 1-mL aliquots of pyrogen-free salinewarmed to 37° C. The recovered lavage fluid is pooled, and the cells arecollected by centrifugation (5,000 rpm, 4° C., 5 minutes) andresuspended in 100 mL of cold PBS. The cells are stained with trypanblue to determine viability, and total nucleated cells are counted usinga hemocytometer.

For differential BAL cell counts, cytospin preparations are made andstained with Diff-Quik (Sysmex, Takatsukadai, Japan). After the samplesare coded, all cytospin preparations are evaluated using an oilimmersion microscope (magnification, ×1,000). At least 200 cells arecounted per preparation, and the absolute number of each cell type iscalculated.

Serum IgG analysis. Serum is obtained from blood taken duringexsanguination of the mice after airway measurement, and 100 μL (1/10dilution in carbonate-bicarbonate buffer) is added to each well of a96-well plate. An IgE-specific enzyme linked immunosorbent assay (ELISA)is used to quantitate total IgE in the serum, using matching antibodypairs (eBioscience) according to the manufacturer's instructions. Forthe ELISA, 96-well plates are first coated overnight with rat anti-mouseIgE (10 μL in 100 μL of PBS; PharMingen, San Diego, Calif., USA), ratanti-mouse IgG1 (20 μg in 100 μL of PBS; PharMingen), or rat anti-mouseIgG2a (20 μg in 100 μL of PBS; PharMingen). The remaining binding sitesare blocked, and the plates are incubated with 100 μL of diluted serum(1:5 for IgE, 1:10 for IgG1 or IgG2a). After the plate is washed, eachof the following is sequentially added, incubated, and removed bywashing: OVA (1 μg/100 μL), peroxidase-labeled rabbit anti-OVA Ig (240ng/100 μL, PharMingen), and 3,3,5,5-tetramethylbenzidine solution (SigmaChemical Co.). The optical density is measured at 450 nm, and the Iglevel is determined relative to that of a reference pool of serum fromOVA-sensitized BALB/c mice (assigned a value of 100 experimentalunits/mL)

Cytokine assays. Commercial preparations of paired antibodies andprotein standards for measurements of mouse IL-4, IL-5, IL-13, and IFN-γ(eBioscience) in sera is used to develop ELISAs according to themanufacturer's instructions.

Lymphocyte proliferation assay. After BAL, the mouse spleen is resected.Mouse splenocytes are separated on a Histopaque (Sigma Chemical Co.)gradient, and the collected cells are washed with PBS. RBCs are lysed bygently mixing the cells with 3.6 mL of 0.24% NaCl for 20 seconds,followed by the quick addition of 0.3 mL of 8.7% NaCl and furtherdilution with PBS. The pellet is suspended in Iscove's ModifiedDulbecco's Medium (IMDM), and stored overnight at 4° C. The nextmorning, the cells are centrifuged at 4° C., suspended in cold PBS,stained with trypan blue, and counted using a hemocytometer.

Splenic T cells are cultured in IMDM supplemented with 25 mM HEPES, 10%(v/v) heat inactivated fetal bovine serum (FBS), 60 mg/L (100 U/mL)penicillin, 100 mg/L streptomycin, and 0.29 g/L L-glutamine. Splenic Tcells are adjusted to 1×10{circumflex over ( )}5 cells/200 μL/well,transferred to 96-well plates, and incubated at 37° C. in a humidified5% CO2 incubator for 72 hours. The cells are stimulated with OVAtreatment (100 μg/mL) for 72 hours. At 12 hours before the end of theincubation, 1 μCi of [3H]-thymidine is added to each well. The cells areharvested onto a glass microfiber filter (Simport, Beloeil, Canada), andradioactivity is measured in a liquid scintillation counter. Theincorporation during the last 12 hours of culture (counts per minute) isused as an index of proliferation.

Flow cytometry. Mouse Treg cells are collected from the spleen andanalyzed for CD4+CD25+Foxp3+ expression using a mouse Treg cell stainingkit containing FITC-labeled anti-CD4, APC-labeled anti-CD25, andPE-labeled anti-Foxp3 (eBioscience) according to the manufacturer'sinstructions. Briefly, prepared cells (1×10{circumflex over ( )}6) arewashed by centrifugation with cold PBS, resuspended in 1 mL offixation/permeabilization solution, and incubated in the dark at 4° C.for 30-60 minutes. The cells are washed once with 2 mL ofpermeabilization buffer, collected by centrifugation, resuspended in 20mL of blocking agent with 2% (2 mL) normal rat serum in permeabilizationbuffer, and incubated at 4° C. for 15 minutes. Next, 20 mL offluorochrome-conjugated antibody or isotype control in permeabilizationbuffer is added, followed by incubation in the dark at 4° C. for 30minutes. Finally, the cells are washed with 2 mL of permeabilizationbuffer, resuspended in flow cytometry buffer (PBS with 2% FBS), andanalyzed by flow cytometry using a FACSCalibur with CellQuest software(BD Biosciences, Mountain View, Calif., USA).

Lung histopathology. For the histological evaluation of lung tissue, theleft lung of each mouse is embedded in paraffin, sectioned to athickness of 5 μm, and stained with hematoxylin and eosin (H&E) toassess eosinophilic infiltration. Inflammation is scored. The degree ofperibronchial and perivascular inflammation is evaluated on a subjectivescale of 0-3. Cellular infiltration in five randomly selected fields isassessed under a Zeiss Axiophot microscope (magnification, ×100; CarlZeiss, Inc., Thornwood, N.Y., USA).

ii. Birch pollen-induced allergic asthma mouse model. Mice receive thefollowing: (i) C. pseudodiphtheriticum, (ii) D. pigrum, or (iii) C.pseudodiphtheriticum and D. pigrum (e.g., from strains listed in Table1, Table 2, and mixtures from Example 1); or (iv) PBS (vehicle)intranasally, eight times on days 1-4 and 8-11 at 5×10{circumflex over( )}8 CFU bacteria/dose, followed by a 2-week asthma induction protocolwith birch pollen extract on alternating days. Effects of preventivetreatment are analyzed based on serum antibody levels, bronchoalveolarlavage cell counts, lung histology, lung cytokine levels, and airwayhyperreactivity. Colonization and translocation of administered bacteriaare assessed by bacterial cell counts in nasal mucosa, fecal samples,cervical lymph nodes, and blood.

Example 7: COPD Model System

COPD is induced by cigarette smoke inhalation of 14 cigarettes per day,twice a day, 7 times/week during 60 days in C57Bl/6 mice. The micereceive bacteria (i) C. pseudodiphtheriticum, (ii) D. pigrum, or (iii)C. pseudodiphtheriticum and D. pigrum (e.g., from strains listed inTable 1, Table 2, and mixtures from Example 1); or (iv) PBS (vehicle) inan amount of 1×10{circumflex over ( )}8 colony-forming units/mouse/day,intranasally at the same time. The pro-inflammatory mediators as IL-6,TNF, IL-1β, CXCL1, CXCL8, CXCL10, KC, CXCL9, CXCL11 andanti-inflammatory as IL-10 in bronchoalveolar lavage fluid (BALF) aremeasured by ELISA. The expression of mRNA of MMP9 and MMP12, NF-1κB,STAT3 and TLR 2, 4 and 9 in lung are analyzed by quantitative RT-PCR.NF-κB is also analyzed by immunolocalization. The lung tissue is forhistological and morphometric analysis.

Example 8: Influenza Model System

Seven-week-old female BALB/c mice are purchased from SLC Co., Ltd(Hamamatsu, Japan). Mice are housed at 23-25° C. with a 12 hourlight/dark cycle and fed standard laboratory rodent feed (OrientalYeast, Tokyo, Japan). Mice are randomly divided into a control group(viral infection only) and an three treatment groups (infected micetreated with (i) C. pseudodiphtheriticum, (ii) D. pigrum, or (iii) C.pseudodiphtheriticum and D. pigrum (e.g., from strains listed in Table1, Table 2, and mixtures from Example 1)). Mice are administered in anamount of 1×10{circumflex over ( )}8 colony-forming units/600μL/mouse/day, intranasally for three days.

The influenza A/PR/8/34 (PR8, H1N1) virus is grown in the allantoic sacsof 11-day-old chicken embryos for 2 days at 34° C. The allantoic fluidis removed and stored at −80° C. The viral titre in allantoic fluid isexpressed as the 50% tissue culture infectious dose (TCID50) for PR8.The PR8 viral titre in allantoic fluid is 10{circumflex over ( )}7.4TCID50/ml.

Mice are infected with the PR8 virus. Briefly, on the day aftercompletion of intranasal administration of treatment bacteria solutionfor three consecutive days, mice are anaesthetized with anintraperitoneal injection of sodium amobarbital (0.25 mg per mouse) andthen infected by dropping 1 μl of PR8 into each nostril (2 μl permouse). To examine the survival of mice inoculated with the PR8solution, 10 μl of PBS (20 μl of PBS per mouse) is administeredintranasally for 3 days after PR8 inoculation. The morbidity andmortality of infected mice are observed for 2 weeks. Morbidity isassessed by ruffling of the fur, slow movement and decreased bodyweight.

Mice are anaesthetized with diethyl ether and killed the next day aftertreatment by exsanguination. Lungs are removed, finely minced andincubated for 90 minutes with 300 U of collagenase (Yakult Honsha Co.,Tokyo, Japan) in 15 ml of RPMI 1640 medium (Sigma, Tokyo, Japan). Todissociate the tissue into single cells, collagenase-treated mincedlungs are gently tapped into a plastic dish. After removal of debris,erythrocytes are depleted by hypotonic lysis. The cells are washed withRPMI medium supplemented with 100 U of penicillin per ml and 100 mg ofstreptomycin per ml and then resuspended in a medium supplemented with10% heat-inactivated foetal calf serum (FCS). Cells are counted usingTrypan Blue exclusion and then resuspended at an appropriateconcentration of 5×10{circumflex over ( )}6 cells per ml.

Isolated lung cells are analyzed for cytotoxic activity in a naturalkiller (NK) cell cytotoxicity assay. Briefly, YAC-1 cells are firstlabelled with 3,3′-dioctadecyloxacarbocyanine perchlorate (Dio)(Molecular Probes, Eugene, Oreg., USA), with a concentration of1.0×10{circumflex over ( )}6 cells 5 per μl and kept for 10 min in a CO2incubator. Dio-labelled YAC-1 cells are then mixed with propidium iodide(PI) (Molecular Probes) at 1.0×10{circumflex over ( )}6 cells 10 per mlRPMI PI 500 per μl. Appropriate numbers of lung cells are added to2×10{circumflex over ( )}4 Dio-labelled and PI-stained YAC-1 cells in96-half-well microtitre plates (Corning, N.Y., USA) in a total volume of0.1 ml of medium containing 10% FCS. The plates are gently centrifugedfor 3 minutes at 750 g and then incubated for 4 hours at 37° C. in 5%CO2. After incubation, the cultured cells are mixed with 400 μl PBS in atube and then analyzed by flow cytometry.

The lungs are removed on day 4. Total RNA is isolated using a FastPureisolation kit (TaKaRa, Ohtsu, Japan). Reverse transcription is carriedout with a PrimeScript RT reagent Kit (TaKaRa). Interferon (IFN)-α,IFN-β, IFN-γ, interleukin (IL)-1β, IL-12, IL-18, tumour necrosis factor(TNF) and monocyte chemotactic protein (MCP)-1 mRNA levels aredetermined using quantitative RT-PCR. Fluorescent reporters are detectedusing a Thermal Cycler Dice Real Time System Single (TaKaRa), andprimers are designed using the Perfect Real Time support system(TaKaRa). Actin-β mRNA levels are determined for all samples tonormalize gene expression. All data are expressed as fold inductioncompared with those obtained for control mice.

Example 9: Idiopathic Pulmonary Fibrosis (IPF) Model System

Eight to 10-week-old C57BL/6J mice are purchased from The JacksonLaboratory and housed under specific pathogen-free conditions. Germ-free(GF) mice on a C57BL/6 background are bred. Oropharyngeal bleomycin isdelivered to mice to elicit acute inflammation (Days 0-7),fibroproliferation (Days 7-14), and fibrosis (Days 14-21). Bleomycintreated mice are randomly divided into a control group (PBS only) andthree treatment groups (bleomycin treated with (i) C.pseudodiphtheriticum, (ii) D. pigrum, or (iii) C. pseudodiphtheriticumand D. pigrum (e.g., from strains listed in Table 1, Table 2, andmixtures from Example 1)). Mice are intranasally administered threetimes, i.e. 20 μl treatment bacteria solution at a concentration of 10mg/ml (200 g per mouse) once daily for three consecutive days. Tissuecollection (including lung), processing, staining is performed. Collagendeposition is measured using a hydroxyproline assay. Genomic DNAextraction from mouse lung tissue and human bronchoalveolar lavage fluidis performed. Pulmonary inflammation in vivo is evaluated by cytokinemeasurements of human BALF and murine lung homogenate using a Luminexplatform (MilliporeSigma).

Example 10: Olfactory Nerve Infection Model System

Bacterial strains. The B. pseudomallei strain MSHR520 is a clinicalisolate from a human case of melioidosis. An allele replacement mutantof MSHR520 lacking capsule (MSHR520ΔCap) is generated. C.pseudodiphtheriticum (Table 1) and D. pigrum (Table 2) clinical isolatesare also prepared.

Mice. S100β-DsRed transgenic reporter mice are obtained in which thehuman S100β promoter drives expression of the DsRed fluorescent proteinsuch that cells that express the S100β promoter express DsRed in thecytoplasm. In these mice, glial cells including olfactory ensheathingcells (OECs) of the olfactory nerve, and Schwann cells of otherperipheral nerves express DsRed protein.

i. Methimazole treatment and intranasal inoculation. 5 to 10 weeks oldS100β-DsRed mice are injected with methimazole (Sigma-Aldrich, 50 mg/kg,10 mg/ml in phosphate buffered saline, PBS) or vehicle (PBS) usingintraperitoneal injection. Three days later, animals are intranasallyinoculated with MSHR520ΔCap or vehicle. A small amount of frozen stock(−80° C. in 20% glycerol; 10-50 μl) is streaked onto LB agar containingstreptomycin (100 μg/ml), incubated at 30° C. for several days, and asingle colony is used to inoculate liquid RB broth and grown withshaking for 16 hour to stationary phase at 37° C. A portion is used forviable count (CFU) determination on LB agar to ensure that the inoculumused is, consistently, a total of 3×10{circumflex over ( )}5 cells whichare resuspend in PBS and delivered as 10 μl droplet/nostril. C.pseudodiphtheriticum and D. pigrum isolates D1-D30 are prepared asdescribed in Example 2 and in a total of 1×10{circumflex over ( )}8cells which are resuspend in PBS and delivered as 10 μl droplet/nostril.Mice are intranasally administered 3 times a day for 3 days: (i) C.pseudodiphtheriticum, (ii) D. pigrum, (iii) D. pigrum C.pseudodiphtheriticum, or (iv) PBS. Five days later, mice areadministered: (i) control (PBS injection+PBS inoculation), (ii)methimazole alone (methimazole injection+PBS inoculation), (iii) B.pseudomallei alone group (PBS injection+B. pseudomallei inoculation),(iv) methimazole+B. pseudomallei group (methimazole injection+B.pseudomallei inoculation).

Animals are housed in individually ventilated hepa-filtered cages(IsoCage N-Biocontainment, Tecniplast) with Aspen wood chip bedding.Animals are provided ad lib food pellets (Standard Rat and Mouse Feed,Specialty Feeds) and water. Environmental conditions within the cagesare maintained at a constant temperature (19-23° C.) and humidity(40-60%) with a 12-hour light and a 12-hour dark cycle.

Tissue preparation. Mice are sacrificed 7 days post intranasalmethimazole/B. pseudomallei inoculation by lethal intraperitonealinjection of sodium pentobarbitone (Lethabarb). Heads are fixed in 4%paraformaldehyde (PFA) in PBS overnight at 4° C., followed bydecalcification in 20% ethylenediaminetetraacetic acid (EDTA) for fourweeks. Heads are embedded in optimal cutting temperature (OCT) medium(ProSciTech) and frozen. Coronal sections (50 m) are cut using acryostat (Leica CM1860).

Immunohistochemistry. Rabbit anti-B. pseudomallei (1:2,000) is used tolabel B. pseudomallei. This antibody is raised against thesarkosyl-insoluble fraction enriched for outer membrane proteins(RRID:AB_2736920). The secondary antibody is donkey anti-rabbit AlexaFluor 488 (Abcam ab150073; 1:300). Class III Beta tubulin is detectedwith rabbit anti-beta III Tubulin (Abcam ab18207; 1:200); the secondaryantibody is donkey anti-rabbit Alexa Fluor 647 (Thermofisher A31573;1:400). Antibodies are diluted in 2% bovine serum albumin (BSA) with0.3% Triton X-100 (TX) in PBS. Cryostat sections are first incubatedwith 2% BSA/TX/PBS for 60 min at room temperature, followed by overnightincubation with primary antibodies at 4° C. Sections are washed andincubated with secondary antibodies for 1 h. Cell nuclei were stainedwith 4′6-diamidino-2-phenylindole (DAPI). Images are captured using anepifluorescence microscope and a laser scanning confocal microscope.Detection of whether bacteria are present in the olfactory epithelium,olfactory nerve and olfactory bulb, is performed.

Example 11: Autism Spectrum Disorder Model System

Mice. Adult mice (2-4 mo) of both sexes are used. The experimentalCntnap2 and Shank3 mice are obtained by breeding heterozygotes withheterozygotes so that litters including wild-type (WT; +/+),heterozygote (HET; +/−), and homozygote (KO; −/−) mice could beobtained. The original breeder mice are available from the JacksonLaboratory (Bozdagi et al. 2010; Poliak et al. 2003).

AAV-GCaMP6 Injection. AAV2/1.Syn.GCaMP6fWPRE.SV40 (Penn Vector Core;titer ˜22×10{circumflex over ( )}13 GC/mL, volume ˜0.1 μL) is injectedinto the dorsal olfactory bulb using a Picospritzer III, according tothe method described by Kuhlman and Huang (2008). A glass pipette (tipsize ˜10 μm) is lowered through a hole in the skull to ˜300 μm below thepial surface; 20 pulses (˜10 ms long) are pressure injected at 0.3 Hz,and then the pipette is retracted 50 μm toward the surface and injectionrepeated as before at each site. This sequence is repeated until thepipette reached ˜50 μm below the surface. This injection protocolresulted in a widespread and dense GCaMP6 expression in cell bodies anddendritic processes in mitral and tufted cells. Virus is allowed toexpress for 2 to 3 weeks after injection before craniotomy and imagingis performed.

The WT and KO mice are randomly divided into a control group (PBS only)and three treatment groups: (i) C. pseudodiphtheriticum, (ii) D. pigrum,or (iii) C. pseudodiphtheriticum and D. pigrum (e.g., from strainslisted in Table 1, Table 2, and mixtures from Example 1). Mice areadministered in an amount of 1×10{circumflex over ( )}8 colony-formingunits/600 μL/mouse/day, intranasally for three days.

In Vivo Two-Photon Calcium Imaging. Mice are anesthetized with ketamine(20 mg/mL)-xylazine (3.3 mg/mL) followed by supplemental ketamine.Reinjection of ketamine (20 mg/mL) is performed every 30 min to maintaina stable level of anesthesia throughout surgery and imaging (6-7 h). Awindow (1 mm×1 mm) is created over the left dorsal olfactory bulb ofmice and covered by no. 1.5 cover glasses (Zeiss) sealed with dentalacrylic. A thin layer of low-melting-point agarose gel is placed inbetween the craniotomy and the cover glass to reduce motion duringimaging. The craniotomy is performed on the same area of the dorsalsurface across animals to ensure consistent placing of the craniotomyand thus sampling of glomeruli. Two-photon imaging of dendriticprocesses in the glomerular layer is performed on head-fixed mice usinga Chameleon Ultra II laser tuned to a wavelength of 935 nm and an invivo two-photon platform from Intelligent Imaging Innovations (3I),through a Zeiss W Plan-apochromatic ×20/1.0 objective. Data analysis ofGCaMP6 activity is only performed within individual glomeruli. Becauseof the widespread expression of GCaMP6 across all layers of mainolfactory bulb (MOB), GCaMP6 activity recorded in the superficialglomeruli is considered population activity and potentially attributedby a variety of cell types. Before each odor presentation, a 1-min-longvideo is captured to assess spontaneous event rate. For each odorpresentation trial, a 20-s-long video capturing 5-s baseline and 15-spoststimulus fluorescence activity is collected in Slidebook5.5 (3I) ata frequency of 4.7 Hz. The imaging field is a resolution of 200×200pixel{circumflex over ( )}2, corresponding to a 520×520-μm{circumflexover ( )}2 window. Positioning of the cranial window under themicroscope is consistent so that similar subareas of the dorsal fieldwere viewed across animals.

Odorant Stimulation. Brief pulses of isoamyl acetate (IAA; 100%saturated vapor, flow rate ˜7.5 L/min) are delivered to the anesthetizedmouse through a custom-built olfactometer to the animal's left nostril.Odor pulses are controlled by valves opened via transistor-transistorlogic pulses (Lee Valves). The distance of the tubing outlet to thenostril (˜5 mm) is maintained throughout each experiment and acrossanimals. Stimuli consisted of a single-pulse of IAA. In initial tests,stimulus duration is varied between 5 and 1,000 ms. Single-trialresponses of multiple glomeruli in the field are obtained for a range ofstimulus durations to construct the relation between the stimulusduration and the fraction of activated glomeruli. In a typicalexperiment, the 200-ms stimulus is presented first followed by the 20-msstimulus, followed by an interval of 1.5-2 minutes for 15 trials.Photoionization detector (PID) measurements of the odor plume arecollected using a MiniRAE 3000 (RAE Systems, Inc., Sunnyvale, Calif.).The PID is placed roughly 5 mm from the end of the tubing. This distanceis to mimic the distance from the tubing to the animal's nostril. PIDmeasurements are digitized at 10 kHz using an ITC-18 (InstruTECH)controlled by custom software written in IgorPro (Wavemetrics).

Example 12: Parkinson's Disease Model System

4-week-old and 2-month-old male C57BL/6 mice. Fifteen mice are employedin each group. All the mice are raised without pathogens, randomly fedwith food and water, and fed in a 12/12-hour light/dark cycle in atemperature control room (25±2° C.) for 1 week before the experimentalmanipulation.

The mice receive bacteria (i) C. pseudodiphtheriticum, (ii) D. pigrum,or (iii) C. pseudodiphtheriticum and D. pigrum (e.g., strains in listedTable 1, Table 2, and mixtures from Example 1); or (iv) PBS (vehicle) inan amount of 1×10{circumflex over ( )}9 colony-forming units/mouse/day,intranasally from one week before MPTP sensitization to the endpoint ofthe study. Mice receive MPTP (Sigma, USA) in an amount of (1mg/nostril). One month after MPTP administration, motor behaviour isanalysed by rotarod test and pole test.

Rotarod Test. All sessions are performed in the range (8 and 12 am). Tolearn how to keep their balance, mice first received a 300 secondtraining session on the slowly rotating rod (16 rpm). 1 hour later, miceare re-placed in the rod, and the time (latency) until a mouse falls offthe rod rotating as being continuously accelerated was measured(increased per 30 seconds, from 16 to 32 rpm in 5 minutes). The combinedmeasures of the rotarod performance of each mouse are yielded as thearea under the mean time curve on the rod against rotation speed(overall rod performance scores, ORP).

Pole Test. For the assessment of bradykinesia in the mice, a pole testis performed. The mouse is placed on top of a vertical rough-surfacedstick (with a diameter of 10 mm, and a height of 58 cm). The time toturn and reach the floor are recorded. Two days before the test, eachmouse is trained to descend the pole. On the day of the test, the micecan practice five times and then three times for up to 4 minute each.

Example 13: Lung Cancer Model System

i. Mouse model Female C57BL/6 mice, aged 6-8 weeks (Charles River), aremaintained in laminar flow rooms at constant temperature and humidity,with food and water given ad libitum. Mice are treated with vancomycinand/or neomycin (5 days/week at 12-hr intervals) or with bacteria ((i)C. pseudodiphtheriticum, (ii) D. pigrum, or (iii) C.pseudodiphtheriticum and D. pigrum) (e.g., strains in listed Table 1,Table 2, and mixtures from Example 1) (3 times/week), starting 2 weeksbefore they are i.v. injected with 5×10{circumflex over ( )}5 B16melanoma cells and continuing throughout the experiment.

For depletion of effector cells, mice are i.v. injected with CD3 F(ab′)2fragments (145-2C11 f(ab′)2) (BioXcell) at a dose of 50 μg/day for 5days/week starting 1 day before tumor injection to deplete T cells orare intraperitoneally (i.p.) injected with 500 μg of α-NK1.1 antibody(PK136) (BioXcell) 1 day before tumor injection, followed by injectionof 200 μg every 5 days throughout the experiment, to deplete NK cells.The efficacy of cell depletion is verified by staining peripheral bloodleukocytes for specific subsets after depletion. In therapeuticexperiments, mice are i.v. injected with 5×10{circumflex over ( )}5 B16melanoma cells and treated starting 7 days after tumor cell injectionwith antibiotics (vancomycin and neomycin) or probiotics ((i) C.pseudodiphtheriticum, (ii) D. pigrum, or (iii) C. pseudodiphtheriticumand D. pigrum) alone or in combination with DTIC, administered i.p. at70 mg/kg (5 days/week). Mice are weighed twice weekly and euthanized atday 21 after tumor injection to count macroscopic lung metastases.

ii. Sheep model. Adult female sheep (Highlander, n=1; Scottishblackface, n=7; Scotch Mule, n=1), weighing 39-65 kg and diagnosed withnaturally-occurring pre-clinical OPA, are obtained. Sheep are bedded onstraw, with ad libitum access to food and water in groups of at least 2animals and were allowed a period of adaptation of at least 24 hourbefore undergoing anesthesia.

Subjects are divided into control group (PBS only), and three treatmentgroups (infected and treated with (i) C. pseudodiphtheriticum, (ii) D.pigrum, or (iii) C. pseudodiphtheriticum and D. pigrum). Subjects areadministered in an amount of 1×10{circumflex over ( )}8 colony-formingunits/600 μL/day, intranasally for three days, followed by a 14 daywashout period. In an additional assays, a similar protocol is followed,with the addition of a chemotherapy to screen for a combinationtherapeutic effect.

Computed Tomography Imaging. A single-section SOMATOM Definition AS 64slice helical CT machine (Siemens Healthcare Ltd, Camberley, UK) is usedfor all advanced imaging procedures.

Histopathology. OPA tissue is fixed for at least 24 h (depending ontissue thickness) in 4% formaldehyde (Genta Medical, UK) beforeundergoing processing using the Thermo Scientific Excelsior AS TissueProcessor (Thermo Scientific, UK) and embedding in paraffin. Tissue issectioned using the Leica RM2235 rotary microtome (Leica MicrosystemsLtd, UK); microtome sections of 4 μm were placed on SuperFrost Plusglass slides (Thermo Scientific, UK) and allowed to dry for a minimum of4 h at 53° C.

For haematoxylin and eosin staining, sections are deparaffinised by 3changes in 100% xylene for 5 min, then rehydrated by placing intoalcohol; 2 changes in 100% ethanol, followed by 80% then 50% for 2 mineach time. The slides are washed in running water for 2 min, beforeplacing in haematoxylin (Shandon Harris Haematoxylin, Thermo Scientific,UK) for a maximum of 10 min. Slides are washed in running water for 2min and then placed into Scott's tap water substitute for a maximum of10 min until the tissue sections turned blue. Sections ae counterstainedby placing them into Eosin Y (Shandon Eosin Y Cytoplasmic Counterstain,Thermo Scientific, UK) for 5 min. The slides are dehydrated by placingthem into alcohol; 50% ethanol for 30 s, 80% ethanol for 30 s, then 2changes in 100% ethanol for 2 min. The slides are placed in xylene for10 min before being mounted with coverslips using DXP mountant(Sigma-Aldrich, UK).

Example 14: Corynebacterium Growth Assay

The following was performed to assay growth rate attributes for C.pseudodiptheriticum strains. 9 mL of Columbia 1% Tween broth wasinoculated with C. pseudodiptheriticum colonies and incubated overnightat 37 degrees Celsius, shaking at 200 rpm. From the overnight culture,an OD600 measurement was taken and 30 mL of fresh Columbia 1% Tweenbroth was inoculated to reach a starting OD600 of 0.04, cultures wereincubated at 37 degrees Celsius shaking at 200 rpm. OD600 measurementswere taken over a 14.5 hour time period. Results of OD600 measurementsfor growth of ATCC 10700 are show in in FIG. 2A, and shown as Log(OD600)for the Y axis in FIG. 2B. As can be seen, the doubling time during logphase (hours 2 to 6) was about 86 minutes. Results of OD600 measurementsfor growth of JCM 1320 are show in in FIG. 3A, and shown as Log(OD600)for the Y axis in FIG. 3B. As can be seen, the doubling time during logphase (hours 2 to 6) was about 129 minutes.

To assay co-culture growth, starting inoculum was varied to achievemixed cultures while maintaining starting OD600 of 0.04. For example,diluting overnight culture to 0.04 for 400 uL for a 75% JCM 1320 25%ATCC 10700 mix, required 300 uL from the JCM 1320 culture and 100 uLfrom the ATCC 10700 culture. OD600 measurements were taken over a 14.5hour time period. Results of OD600 measurements for growth are shown inin FIG. 4A, where samples A, B, C, D, and E are 100% ATCC 10700, 25% JCM1320 and 75% ATCC 10700, 50% JCM 1320 and 50% ATCC 10700, 75% JCM 1320and 25% ATCC 10700, and 100% JCM 1320, respectively. Results ofLog(OD600) measurements for growth are shown in in FIG. 4B, with thesame sample order ordering of data trendlines as in FIG. 4A. Doublingtimes were as follows: 100% ATCC 10700 [86 minutes], 25% JCM 1320 and75% ATCC 10700 [89 minutes], 50% JCM 1320 and 50% ATCC 10700 [91minutes], 75% JCM 1320 and 25% ATCC 10700 [98 minutes], and 100% JCM1320 [129 minutes]. Doubling time appeared primarily driven by the ATCC10700 strain. Final stationary phase cell density of mixed cultures waswithin similar range (OD₆₀₀±0.1).

Example 15: Consortia Growth Assays

The following was performed to assay co-culture attributes for strainsof C. pseudodiptheriticum. First, a direct co-culture of C.pseudodiptheriticum strains ATCC 10700 and JCM 1320 was performed. BothC. pseudodiptheriticum strains were spotted in close proximity at thesame time on a Columbia 1% Tween agar plate: four spottings of ATCC10700 on the left, and for spottings of JCM 1320 on the right. An imagecapture was taken after 24 hours from spotting, as shown in FIG. 5 . Ascan be seen in FIG. 5 , the cultures do not display features ofantagonism between the different strains. This is an unexpected result,as co-culturing of C. pseudodiptheriticum clinical isolates has not beenreported to date.

Second, a direct co-culture of C. pseudodiptheriticum strain ATCC 10700or JCM 1320, and D. pigrum was performed. An image capture was takenafter 24 hours from spotting, as shown in FIG. 6 . Referring to FIG. 6 ,on the left is a column after two spottings of ATCC 10700 and just tothe right of that is a column after two spottings of D. pigrum. On theright of the image is a column after two spottings of D. pigrum and justto the right of that is a column after two spottings of JCM 1320. As canbe seen in FIG. 6 , the cultures do not display features of antagonismbetween the different strains.

While some embodiments of the present invention have been shown anddescribed herein, it will be obvious to those skilled in the art thatsuch embodiments are provided by way of example only. Numerousvariations, changes, and substitutions will now occur to those skilledin the art without departing from the invention. It should be understoodthat various alternatives to the embodiments of the invention describedherein may be employed in practicing the invention. It is intended thatthe following claims define the scope of the invention and that methodsand structures within the scope of these claims and their equivalents becovered thereby.

What is claimed is:
 1. A pharmaceutical composition comprising: a live,purified population of bacteria comprising: at least three differentstrains of Dolosigranulum pigrum, wherein the at least three differentstrains of Dolosigranulum pigrum provide various bactericidalmechanisms, wherein the at least three different strains ofDolosigranulum pigrum are a lyophilized population of bacteria, whereinthe at least three different strains of Dolosigranulum pigrum arepresent in a total amount of at least 10{circumflex over ( )}3 CFU, andwherein two strains of the at least three different strains ofDolosigranulum pigrum are present individually in an amount of up toabout 40% of total CFUs for CFUs present in the live, purifiedpopulation of bacteria; and a pharmaceutically acceptable excipient. 2.The pharmaceutical composition of claim 1, wherein the pharmaceuticalcomposition is in a nasal spray bottle.
 3. The pharmaceuticalcomposition of claim 1, wherein at least one of the at least threedifferent strains of Dolosigranulum pigrum is a strain selected from thegroup consisting of Dolosigranulum pigrum deposited under accessionnumbers LMG P-31124 and LMG P-31154.
 4. The pharmaceutical compositionof claim 3, wherein the pharmaceutical composition is in a nasal spraybottle.
 5. The pharmaceutical composition of claim 1, wherein the live,purified population of bacteria is present in the total amount of up to10{circumflex over ( )}15 CFU.
 6. The pharmaceutical composition ofclaim 1, wherein the live, purified population of bacteria is present inthe total amount of 10{circumflex over ( )}3 to 10{circumflex over( )}12 CFU.
 7. The pharmaceutical composition of claim 1, wherein thelive, purified population of bacteria comprises up to 10 strains.
 8. Thepharmaceutical composition of claim 1, wherein the various bactericidalmechanisms are directed to S. aureus.
 9. The pharmaceutical compositionof claim 1, wherein the live, purified population of bacteria comprises4 or 5 strains.